Li Zhang, Wen Zhao, Hongsheng Yang, Tingting Deng, Yugang Li
Background
Intervertebral disc degeneration (IDD) is a prevalent spinal condition frequently associated with pain and motor impairment, imposing a substantial burden on quality of life. Despite extensive investigations into the genetic predisposition to IDD, the precise pathogenic genes and molecular pathways involved remain inadequately characterized, underscoring the need for continued research to clarify its genetic underpinnings.
Methods
This study leveraged IDD data from the FinnGen R12 cohort and integrated expression quantitative trait loci data across 49 tissues from the Genotype-Tissue Expression version 8 database to perform a cross-tissue transcriptome-wide association study (TWAS). The analytical framework incorporated functional summary-based imputation (FUSION), unified test for molecular signatures (UTMOST), and gene-level analysis via multi-marker genome annotation (MAGMA). To substantiate the findings, Mendelian randomization (MR) and colocalization analyses were subsequently conducted.
Results
Through TWAS and MAGMA analyses, 33 susceptibility genes associated with IDD were identified. Subsequent MR and colocalization analyses refined this list to six candidate genes—ADD1, GFPT1, MAPRE3, MSANTD1, SLC30A6, and XBP1—which may contribute to the initiation and progression of IDD by modulating pathways implicated in the endoplasmic reticulum stress response.
Conclusion
Six susceptibility genes associated with the risk of IDD were identified in this study, offering novel insights into the genetic architecture and potential pathogenic pathways underpinning the development of IDD.
{"title":"A Cross-Tissue Transcriptome-Wide Association Study Identified Susceptibility Genes for Intervertebral Disc Degeneration","authors":"Li Zhang, Wen Zhao, Hongsheng Yang, Tingting Deng, Yugang Li","doi":"10.1002/jsp2.70109","DOIUrl":"https://doi.org/10.1002/jsp2.70109","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Intervertebral disc degeneration (IDD) is a prevalent spinal condition frequently associated with pain and motor impairment, imposing a substantial burden on quality of life. Despite extensive investigations into the genetic predisposition to IDD, the precise pathogenic genes and molecular pathways involved remain inadequately characterized, underscoring the need for continued research to clarify its genetic underpinnings.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This study leveraged IDD data from the FinnGen R12 cohort and integrated expression quantitative trait loci data across 49 tissues from the Genotype-Tissue Expression version 8 database to perform a cross-tissue transcriptome-wide association study (TWAS). The analytical framework incorporated functional summary-based imputation (FUSION), unified test for molecular signatures (UTMOST), and gene-level analysis via multi-marker genome annotation (MAGMA). To substantiate the findings, Mendelian randomization (MR) and colocalization analyses were subsequently conducted.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Through TWAS and MAGMA analyses, 33 susceptibility genes associated with IDD were identified. Subsequent MR and colocalization analyses refined this list to six candidate genes—ADD1, GFPT1, MAPRE3, MSANTD1, SLC30A6, and XBP1—which may contribute to the initiation and progression of IDD by modulating pathways implicated in the endoplasmic reticulum stress response.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Six susceptibility genes associated with the risk of IDD were identified in this study, offering novel insights into the genetic architecture and potential pathogenic pathways underpinning the development of IDD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70109","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145012296","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ossification of the posterior longitudinal ligament (OPLL) is a pathological condition characterized by ectopic ossification of spinal ligaments, primarily driven by abnormal osteogenic differentiation of ligament fibroblasts with stem cell-like properties. The SOX transcription factor family is crucial in regulating cell stemness and differentiation. Among them, SOX8 is known to influence osteoblast differentiation, but its role in OPLL remains unclear.
Methods
SOX8 expression was analyzed in non-OPLL and OPLL ligament tissues and cells. Its role in osteogenic differentiation was assessed using ALP/Alizarin Red staining, qPCR, Western blotting, and subcutaneous ectopic ossification models in nude mice. Mass spectrometry and co-immunoprecipitation identified SOX8-interacting E3 ubiquitin ligases, with ubiquitination assays assessing their effects on SOX8 stability. RNA-seq, GTRD analysis, and dual-luciferase reporter assays revealed SOX8 target genes. Functional recovery experiments were conducted to explore the role of these interactions in the osteogenic differentiation of ligament fibroblasts.
Results
SOX8 expression was downregulated in OPLL ligament tissues and cells. Functional analyses showed that SOX8 inhibits osteogenic differentiation of ligament fibroblasts both in vitro and in vivo. Mechanistically, TRIM25, an E3 ubiquitin ligase, was found to interact with SOX8, promoting its ubiquitination and degradation. Rescue experiments showed that SOX8 knockdown or overexpression reversed the osteogenic effects of TRIM25 knockdown or overexpression in ligament fibroblasts. Additionally, OSR2 was identified as a transcriptional target of SOX8, with SOX8 promoting OSR2 transcription. OSR2 knockdown negated the inhibitory effects of SOX8 overexpression on osteogenic differentiation.
Conclusions
SOX8 serves as a critical negative regulator of osteogenic differentiation in ligament fibroblasts. TRIM25 promotes ectopic ossification in OPLL by enhancing SOX8 ubiquitination and degradation, while SOX8 inhibits osteogenic differentiation through transcriptional activation of OSR2. These findings highlight the TRIM25/SOX8/OSR2 axis as a key regulator in OPLL ectopic ossification, suggesting it to be a potential target for non-surgical treatment.
{"title":"TRIM25-Mediated Ubiquitination and Degradation of SOX8 Promotes Ligament Fibroblast Osteogenic Differentiation and Regulates OPLL Progression by Inhibiting OSR2 Transcription","authors":"Zhenqiang Wang, Yifan Tang, Changjiang Gu, Minming Lu, Ziheng Wei, Quanwei Zhou, Shengyuan Zhou, Xiongsheng Chen","doi":"10.1002/jsp2.70112","DOIUrl":"https://doi.org/10.1002/jsp2.70112","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Ossification of the posterior longitudinal ligament (OPLL) is a pathological condition characterized by ectopic ossification of spinal ligaments, primarily driven by abnormal osteogenic differentiation of ligament fibroblasts with stem cell-like properties. The SOX transcription factor family is crucial in regulating cell stemness and differentiation. Among them, SOX8 is known to influence osteoblast differentiation, but its role in OPLL remains unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>SOX8 expression was analyzed in non-OPLL and OPLL ligament tissues and cells. Its role in osteogenic differentiation was assessed using ALP/Alizarin Red staining, qPCR, Western blotting, and subcutaneous ectopic ossification models in nude mice. Mass spectrometry and co-immunoprecipitation identified SOX8-interacting E3 ubiquitin ligases, with ubiquitination assays assessing their effects on SOX8 stability. RNA-seq, GTRD analysis, and dual-luciferase reporter assays revealed SOX8 target genes. Functional recovery experiments were conducted to explore the role of these interactions in the osteogenic differentiation of ligament fibroblasts.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>SOX8 expression was downregulated in OPLL ligament tissues and cells. Functional analyses showed that SOX8 inhibits osteogenic differentiation of ligament fibroblasts both in vitro and in vivo. Mechanistically, TRIM25, an E3 ubiquitin ligase, was found to interact with SOX8, promoting its ubiquitination and degradation. Rescue experiments showed that SOX8 knockdown or overexpression reversed the osteogenic effects of TRIM25 knockdown or overexpression in ligament fibroblasts. Additionally, OSR2 was identified as a transcriptional target of SOX8, with SOX8 promoting OSR2 transcription. OSR2 knockdown negated the inhibitory effects of SOX8 overexpression on osteogenic differentiation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>SOX8 serves as a critical negative regulator of osteogenic differentiation in ligament fibroblasts. TRIM25 promotes ectopic ossification in OPLL by enhancing SOX8 ubiquitination and degradation, while SOX8 inhibits osteogenic differentiation through transcriptional activation of OSR2. These findings highlight the TRIM25/SOX8/OSR2 axis as a key regulator in OPLL ectopic ossification, suggesting it to be a potential target for non-surgical treatment.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70112","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144998973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
This study explores the therapeutic potential of extracellular vesicles (EVs) derived from Wharton's Jelly mesenchymal stem cells in an in vitro 3D model of intervertebral disc degeneration under inflammatory stress. The treatment with WJ-MSC-EVs enhanced nucleus pulposus cell proliferation, viability, and extracellular matrix synthesis while reducing oxidative stress and catabolic gene expression. These results support the promise of WJ-MSC-EVs as a novel, cell-free strategy for disc regeneration in inflammatory conditions.
{"title":"Wharton's Jelly Mesenchymal Stromal Cell-Derived Extracellular Vesicles Attenuate Intervertebral Disc Degeneration Under Inflammatory Stress in an In Vitro 3D Culture System","authors":"Veronica Tilotta, Gianluca Vadalà, Giuseppina Di Giacomo, Luca Ambrosio, Claudia Cicione, Fabrizio Russo, Adas Darinskas, Rocco Papalia, Vincenzo Denaro","doi":"10.1002/jsp2.70106","DOIUrl":"https://doi.org/10.1002/jsp2.70106","url":null,"abstract":"<p>This study explores the therapeutic potential of extracellular vesicles (EVs) derived from Wharton's Jelly mesenchymal stem cells in an in vitro 3D model of intervertebral disc degeneration under inflammatory stress. The treatment with WJ-MSC-EVs enhanced nucleus pulposus cell proliferation, viability, and extracellular matrix synthesis while reducing oxidative stress and catabolic gene expression. These results support the promise of WJ-MSC-EVs as a novel, cell-free strategy for disc regeneration in inflammatory conditions.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70106","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144869879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Michael J. Schneider, Carol M. Greco, Amanda M. Acevedo, Kevin M. Bell, Jessa Darwin, Anthony Delitto, Nathan E. Dodds, John M. Jakicic, Gina P. McKernan, Charity G. Patterson, Paul A. Pilkonis, Sara R. Piva, Gwendolyn A. Sowa, Nam V. Vo, Lan Yu, Ajay D. Wasan
Background
Quantitative Sensory Testing (QST), also known as psychophysical testing, includes standardized methods for assessing humans' perceptions of different types of sensory stimuli and their associated pain thresholds. QST results can be used to estimate altered or atypical sensory processing and thus can be useful for determining pain mechanisms such as nociplastic or central nervous system-mediated pain. The University of Pittsburgh Mechanistic Research Center, entitled, “Low Back Pain: Biological, Biomechanical, Behavioral Phenotypes (LB3P),” is part of the National Institutes of Health's Helping to End Addiction Long-term Initiative. LB3P conducted a prospective, observational cohort study to identify phenotypes of over 1000 participants with cLBP. QST was conducted on these participants as part of comprehensive data collection. This article reports on the results of the QST procedures performed at the initial in-person enrollment visit.
Methods
Four QST procedures were administered to participants of the LB3P study at their enrollment visit: (1) Pressure Pain Thresholds (PPT) over the participant-reported site of lumbar pain (paraspinals) and a control site (trapezius) using an analog algometer; (2) Temporal Summation (TS) over the lumbar pain and control sites (forearm) using a Neuropen with a 40-g monofilament; (3) Conditioned Pain Modulation (CPM) using a cold water (5°C) immersion tank; and (4) Cold Water Tolerance time. A subset of LB3P participants was excluded from the CPM and cold-water immersion procedures due to medical comorbidities such as cardiovascular disease and diabetic neuropathy. Means and standard deviations (SDs) were calculated from three trials of PPT and TS, two trials of CPM, and one trial of cold-water immersion time. TS was calculated by subtracting the numeric pain scores (0–10 scale) of the first from the 10th pinpricks. CPM was calculated by subtracting the mean trapezius algometer readings during the PPT procedure from those of the trapezius PPT during cold-water immersion.
Results
The final cohort of QST participants was 999 adults. The mean/SD of lumbar and trapezius PPTs was 4.6 (2.4) and 4.4 (1.9) kg/cm2, respectively. The mean/SD of lumbar and forearm TS was 1.6 (2.0) and 1.2 (1.8). Lingering pain after the 10th pinprick (after-sensations) was reported by 19.3% and 15.6% of participants after a series of 10 pinpricks was applied to the lumbar pain site and control site, respectively. The mean/SD CPM was 0.9 (1.2) with a wide range of CPM values
{"title":"Quantitative Sensory Testing in an Observational Cohort of Adults With Chronic Low Back Pain","authors":"Michael J. Schneider, Carol M. Greco, Amanda M. Acevedo, Kevin M. Bell, Jessa Darwin, Anthony Delitto, Nathan E. Dodds, John M. Jakicic, Gina P. McKernan, Charity G. Patterson, Paul A. Pilkonis, Sara R. Piva, Gwendolyn A. Sowa, Nam V. Vo, Lan Yu, Ajay D. Wasan","doi":"10.1002/jsp2.70103","DOIUrl":"https://doi.org/10.1002/jsp2.70103","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Quantitative Sensory Testing (QST), also known as psychophysical testing, includes standardized methods for assessing humans' perceptions of different types of sensory stimuli and their associated pain thresholds. QST results can be used to estimate altered or atypical sensory processing and thus can be useful for determining pain mechanisms such as nociplastic or central nervous system-mediated pain. The University of Pittsburgh Mechanistic Research Center, entitled, “Low Back Pain: Biological, Biomechanical, Behavioral Phenotypes (LB<sup>3</sup>P),” is part of the National Institutes of Health's Helping to End Addiction Long-term Initiative. LB<sup>3</sup>P conducted a prospective, observational cohort study to identify phenotypes of over 1000 participants with cLBP. QST was conducted on these participants as part of comprehensive data collection. This article reports on the results of the QST procedures performed at the initial in-person enrollment visit.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Four QST procedures were administered to participants of the LB<sup>3</sup>P study at their enrollment visit: (1) Pressure Pain Thresholds (PPT) over the participant-reported site of lumbar pain (paraspinals) and a control site (trapezius) using an analog algometer; (2) Temporal Summation (TS) over the lumbar pain and control sites (forearm) using a Neuropen with a 40-g monofilament; (3) Conditioned Pain Modulation (CPM) using a cold water (5°C) immersion tank; and (4) Cold Water Tolerance time. A subset of LB<sup>3</sup>P participants was excluded from the CPM and cold-water immersion procedures due to medical comorbidities such as cardiovascular disease and diabetic neuropathy. Means and standard deviations (SDs) were calculated from three trials of PPT and TS, two trials of CPM, and one trial of cold-water immersion time. TS was calculated by subtracting the numeric pain scores (0–10 scale) of the first from the 10th pinpricks. CPM was calculated by subtracting the mean trapezius algometer readings during the PPT procedure from those of the trapezius PPT during cold-water immersion.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The final cohort of QST participants was 999 adults. The mean/SD of lumbar and trapezius PPTs was 4.6 (2.4) and 4.4 (1.9) kg/cm<sup>2</sup>, respectively. The mean/SD of lumbar and forearm TS was 1.6 (2.0) and 1.2 (1.8). Lingering pain after the 10th pinprick (after-sensations) was reported by 19.3% and 15.6% of participants after a series of 10 pinpricks was applied to the lumbar pain site and control site, respectively. The mean/SD CPM was 0.9 (1.2) with a wide range of CPM values ","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70103","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144869839","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Daniele Zuncheddu, Paola Buedo, Martin J. Stoddart, Laura B. Creemers, Sibylle Grad, Marcin Waligora
Background
Intervertebral disc degeneration (IDD) and osteoarthritis (OA) share many similarities in the molecular processes involved in the onset and progression of these musculoskeletal pathologies. Biological sex is a risk factor for both conditions. Sex bias in orthopedic preclinical research affects knowledge, reproducibility, and translational aspects of basic research. This article aims to provide a comprehensive overview of how donor sex is reported in IDD and OA preclinical research using human or animal samples and in vivo models.
Methods
We performed a cross-sectional study, searching original articles from journals with the highest impact factor in the field, to determine: (i) whether they report donor sex, and if so, whether they include this data in the analysis; and (ii) whether journals have requirements for sex reporting.
Results
Our research has four main outcomes. First, donor sex was reported in only 61.9% of the 284 cases examined. Second, among the studies where sex was reported (176), samples were predominantly from only male donors or animals (56%). Moreover, sex was rarely incorporated as a variable in outcome analysis (3.4% of cases). Finally, although 14 out of 23 journals stipulated sex reporting requirements, 37.7% of papers published in these journals failed to report donor sex.
Conclusions
Our results provide evidence for the under-reporting of sample donor sex in OA and IDD research, which may contribute to the poor translation to clinical efficacy and the replication crisis. Our findings could guide journal policies, institutional guidelines for preclinical research, and funder requirements.
{"title":"Biological Sex Is Under-Reported in Cartilage-Related Preclinical Research: A Cross-Sectional Analysis","authors":"Daniele Zuncheddu, Paola Buedo, Martin J. Stoddart, Laura B. Creemers, Sibylle Grad, Marcin Waligora","doi":"10.1002/jsp2.70104","DOIUrl":"https://doi.org/10.1002/jsp2.70104","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Intervertebral disc degeneration (IDD) and osteoarthritis (OA) share many similarities in the molecular processes involved in the onset and progression of these musculoskeletal pathologies. Biological sex is a risk factor for both conditions. Sex bias in orthopedic preclinical research affects knowledge, reproducibility, and translational aspects of basic research. This article aims to provide a comprehensive overview of how donor sex is reported in IDD and OA preclinical research using human or animal samples and in vivo models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We performed a cross-sectional study, searching original articles from journals with the highest impact factor in the field, to determine: (i) whether they report donor sex, and if so, whether they include this data in the analysis; and (ii) whether journals have requirements for sex reporting.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our research has four main outcomes. First, donor sex was reported in only 61.9% of the 284 cases examined. Second, among the studies where sex was reported (176), samples were predominantly from only male donors or animals (56%). Moreover, sex was rarely incorporated as a variable in outcome analysis (3.4% of cases). Finally, although 14 out of 23 journals stipulated sex reporting requirements, 37.7% of papers published in these journals failed to report donor sex.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our results provide evidence for the under-reporting of sample donor sex in OA and IDD research, which may contribute to the poor translation to clinical efficacy and the replication crisis. Our findings could guide journal policies, institutional guidelines for preclinical research, and funder requirements.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70104","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144861745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
James Melrose, Stone Sima, Neha Chopra, Ashish Diwan, Zi Gu
<div> <section> <h3> Background</h3> <p>One of the significant putative causes of low back pain (LBP) is degeneration of the intervertebral disc (IVD). Degenerated discs exhibit loss of proteoglycans, notably aggrecan, leading to mechanical dysfunction and aberrant nerve ingrowth. This pathological innervation results in the proliferation of nociceptive and mechanoreceptive neurons, significantly contributing to persistent pain. A critical therapeutic target is the dorsal root ganglion (DRG), which serves as a key neural hub for nociceptive signaling and neurogenic inflammation. Increased calcium influx through voltage-gated calcium channels within DRG neurons underpins heightened neuronal excitability, facilitating persistent pain transmission. Recent evidence highlights the promising role of bioactive peptides derived from reptilian and insect venoms as potent calcium channel blockers.</p> </section> <section> <h3> Methods</h3> <p>This conceptual review explores published evidence and mechanistic rationale on naturally occurring toxins and venoms as peptide calcium channel blockers for chronic LBP. We considered DRG targeted mechanisms and delivery approaches, including incorporation into biomimetic proteoglycans for localized, sustained intradiscal release, and their use along conventional nerve block procedures.</p> </section> <section> <h3> Results</h3> <p>Venom derived peptide families including ω-conotoxins from cone snail and Tx3-family spider peptides from Phoneutria nigriventer selectively block neuronal calcium channels (notably Ca<sub>v</sub>2.2), thereby reducing the release of neurotransmitters that propogate pain signals. Alongside these antinocicpetive effects, the targeted mechanism of action and directed modalities of these peptides offer a novel therapeutic approach with potential advantages over tradiitonal analgesics, which often present challenges related to tolerance and systemic side effects.</p> </section> <section> <h3> Conclusion</h3> <p>Naturally occurring bioactive peptide calcium channel blockers delivered either directly to the DRG or through a multifaceted therapeutic approach with biomimetic proteoglycans into the IVD or conventional nerve block procedures into the epidural space resents a promising future direction in managing chronic LBP. This approach warrants further pre-clinical and clinical evaluation to clarify clinical utility, potentially transforming pain management paradigms and significantly reducing healthcare burdens associated with chronic spinal disorders.</p> </section> </
{"title":"A Conceptual Review of Naturally Occurring Toxins and Venoms as Peptide Blockers to Combat Chronic Low Back Pain","authors":"James Melrose, Stone Sima, Neha Chopra, Ashish Diwan, Zi Gu","doi":"10.1002/jsp2.70107","DOIUrl":"https://doi.org/10.1002/jsp2.70107","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>One of the significant putative causes of low back pain (LBP) is degeneration of the intervertebral disc (IVD). Degenerated discs exhibit loss of proteoglycans, notably aggrecan, leading to mechanical dysfunction and aberrant nerve ingrowth. This pathological innervation results in the proliferation of nociceptive and mechanoreceptive neurons, significantly contributing to persistent pain. A critical therapeutic target is the dorsal root ganglion (DRG), which serves as a key neural hub for nociceptive signaling and neurogenic inflammation. Increased calcium influx through voltage-gated calcium channels within DRG neurons underpins heightened neuronal excitability, facilitating persistent pain transmission. Recent evidence highlights the promising role of bioactive peptides derived from reptilian and insect venoms as potent calcium channel blockers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This conceptual review explores published evidence and mechanistic rationale on naturally occurring toxins and venoms as peptide calcium channel blockers for chronic LBP. We considered DRG targeted mechanisms and delivery approaches, including incorporation into biomimetic proteoglycans for localized, sustained intradiscal release, and their use along conventional nerve block procedures.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Venom derived peptide families including ω-conotoxins from cone snail and Tx3-family spider peptides from Phoneutria nigriventer selectively block neuronal calcium channels (notably Ca<sub>v</sub>2.2), thereby reducing the release of neurotransmitters that propogate pain signals. Alongside these antinocicpetive effects, the targeted mechanism of action and directed modalities of these peptides offer a novel therapeutic approach with potential advantages over tradiitonal analgesics, which often present challenges related to tolerance and systemic side effects.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Naturally occurring bioactive peptide calcium channel blockers delivered either directly to the DRG or through a multifaceted therapeutic approach with biomimetic proteoglycans into the IVD or conventional nerve block procedures into the epidural space resents a promising future direction in managing chronic LBP. This approach warrants further pre-clinical and clinical evaluation to clarify clinical utility, potentially transforming pain management paradigms and significantly reducing healthcare burdens associated with chronic spinal disorders.</p>\u0000 </section>\u0000 </","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70107","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144843559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alaina L. Falck, Erick O. Buko, Kayla L. Chase, Diana Pendleton, Katie McDermott, Olivia Kim, Suhail P. Parvaze, Alexandra R. Armstrong, Susan A. Arnold, Elizabeth W. Bradley, Arin M. Ellingson, Christopher P. Ober, Aaron Rendahl, Casey P. Johnson
Background
Client-owned dogs presenting clinically with intervertebral disc disease (IVDD) are a potential comparative animal model to help advance the understanding of disc degeneration and its treatment. To utilize dog patients as a model, noninvasive imaging techniques are needed that can characterize subtle and progressive changes in disc health in longitudinal and treatment efficacy studies. The purpose of this study was to assess the sensitivity of quantitative MRI techniques in detecting disc degeneration in client-owned, nonchondrodystrophic-breed dogs.
Methods
Thoracolumbar vertebral columns from the donated bodies of 15 dogs without a history of IVDD were imaged at 3T MRI. Quantitative MRI maps (T2, T2*, T1ρ, adiabatic T1ρ, adiabatic T2ρ, and ADC) were acquired axially for 10 discs (T11-T12 to L7-S1), and median values were measured in the nucleus pulposus and annulus fibrosus. Four disc health measures (Pfirrmann grade, histology score, water content, and glycosaminoglycan content) were evaluated for each disc. The quantitative MRI and disc health measures were compared using linear models, and partial correlations (Rpartial) were calculated.
Results
Most dogs had both relatively healthy and degenerated discs as assessed by Pfirrmann grade and histology score. Quantitative MRI values in relatively healthy discs varied greatly between dogs but were similar across disc levels. In the nucleus pulposus, T2 relaxation times were moderately correlated with Pfirrmann grade (Rpartial = −0.62; p < 0.0001), histology score (Rpartial = −0.63; p < 0.0001), and water content (Rpartial = +0.45; p < 0.0001), and weakly correlated with glycosaminoglycan content (Rpartial = +0.31; p = 0.0047). T2, T2*, T1ρ, adiabatic T1ρ, and adiabatic T2ρ had similar relationships to the disc health measures in the nucleus pulposus. No notable relationships were observed with ADC or in the annulus fibrosus.
Conclusions
Quantitative T2, T2*, T1ρ, adiabatic T1ρ, and adiabatic T2ρ relaxation time mapping techniques are similarly related to radiological and histological measures of disc health and water and glycosaminoglycan content in nonchondrodystrophic-breed dogs.
{"title":"Relationship Between Quantitative MRI and Radiological, Histological, and Biochemical Measures of Intervertebral Disc Health in Client-Owned, Nonchondrodystrophic-Breed Dogs","authors":"Alaina L. Falck, Erick O. Buko, Kayla L. Chase, Diana Pendleton, Katie McDermott, Olivia Kim, Suhail P. Parvaze, Alexandra R. Armstrong, Susan A. Arnold, Elizabeth W. Bradley, Arin M. Ellingson, Christopher P. Ober, Aaron Rendahl, Casey P. Johnson","doi":"10.1002/jsp2.70105","DOIUrl":"https://doi.org/10.1002/jsp2.70105","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Client-owned dogs presenting clinically with intervertebral disc disease (IVDD) are a potential comparative animal model to help advance the understanding of disc degeneration and its treatment. To utilize dog patients as a model, noninvasive imaging techniques are needed that can characterize subtle and progressive changes in disc health in longitudinal and treatment efficacy studies. The purpose of this study was to assess the sensitivity of quantitative MRI techniques in detecting disc degeneration in client-owned, nonchondrodystrophic-breed dogs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Thoracolumbar vertebral columns from the donated bodies of 15 dogs without a history of IVDD were imaged at 3T MRI. Quantitative MRI maps (T2, T2*, T1ρ, adiabatic T1ρ, adiabatic T2ρ, and ADC) were acquired axially for 10 discs (T11-T12 to L7-S1), and median values were measured in the nucleus pulposus and annulus fibrosus. Four disc health measures (Pfirrmann grade, histology score, water content, and glycosaminoglycan content) were evaluated for each disc. The quantitative MRI and disc health measures were compared using linear models, and partial correlations (<i>R</i><sub>partial</sub>) were calculated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Most dogs had both relatively healthy and degenerated discs as assessed by Pfirrmann grade and histology score. Quantitative MRI values in relatively healthy discs varied greatly between dogs but were similar across disc levels. In the nucleus pulposus, T2 relaxation times were moderately correlated with Pfirrmann grade (<i>R</i><sub>partial</sub> = −0.62; <i>p</i> < 0.0001), histology score (<i>R</i><sub>partial</sub> = −0.63; <i>p</i> < 0.0001), and water content (<i>R</i><sub>partial</sub> = +0.45; <i>p</i> < 0.0001), and weakly correlated with glycosaminoglycan content (<i>R</i><sub>partial</sub> = +0.31; <i>p</i> = 0.0047). T2, T2*, T1ρ, adiabatic T1ρ, and adiabatic T2ρ had similar relationships to the disc health measures in the nucleus pulposus. No notable relationships were observed with ADC or in the annulus fibrosus.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Quantitative T2, T2*, T1ρ, adiabatic T1ρ, and adiabatic T2ρ relaxation time mapping techniques are similarly related to radiological and histological measures of disc health and water and glycosaminoglycan content in nonchondrodystrophic-breed dogs.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70105","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144833055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Carol M. Greco, Nathan E. Dodds, Amanda M. Acevedo, William Anderst, Kevin M. Bell, Jessa Darwin, Anthony Delitto, John M. Jakicic, Gina P. McKernan, Charity G. Patterson, Paul A. Pilkonis, Sara R. Piva, Michael J. Schneider, Nam V. Vo, Ajay D. Wasan, Lan Yu, Gwendolyn A. Sowa
Background
Chronic low back pain (cLBP) is complex, disabling, and costly to patients and to society. Patients' social circumstances, beliefs, and behaviors interact in a dynamic way with biomedical factors and have the potential to amplify or reduce suffering. It is important to assess the experience of pain via patient-reported outcomes (PROs). The University of Pittsburgh Mechanistic Research Center, entitled, “Low Back Pain: Biological, Biomechanical, Behavioral Phenotypes (LB3P),” is part of the National Institutes of Health's Helping to End Addiction Long-term Initiative. LB3P conducted a prospective, observational cohort study to identify phenotypes of over 1000 participants with cLBP. This article reports key information from the PROs and selected demographic variables obtained at the in-person LB3P study enrollment visit.
Methods
The LB3P study participants completed numerous PROs, including the minimum data set assessments of the NIH Research Task Force on back pain and the NIH HEAL Initiative's Common Data Elements. PROs were organized into five conceptual domains: (1) Pain Characteristics and Qualities, (2) Pain-related Psychosocial Factors, (3) General Psychosocial Factors, (4) General Health and Lifestyle Factors, and (5) Social Determinants of Health (SDoH). Patient Acceptance of Symptom Status, which consists of yes/no responses to 10 questions about whether the level of each of the 10 symptoms is satisfactory, was also assessed.
Results
PRO measures were collected from 1007 LB3P participants with cLBP. The means and standard deviations, or medians and interquartile ranges, and percentages for the PRO variables collected at the in-person enrollment visit are presented for the overall group and stratified by sex at birth (females and males) and by age (< 60 years old and ≥ 60 years old). For the participants overall, and across sex and age groups, pain intensity and interference were moderate on average. Neuropathic pain, assessed via PainDETECT, was present in 18% of the overall sample, and in 22.5% of those younger than 60. On average, fatigue, depressive and anxiety symptoms, memory and concentration, self-efficacy, and positive outlook were within normal limits, as indicated by PROMIS T-scores. However, PROMIS Physical function was below normal, with T-scores in the mild to moderate range of impairment. When participants were asked to rate the acceptability of their symptom status in 10 areas of function, the most frequently reported areas of dissatisfacti
{"title":"Patient-Reported Outcomes Among an Observational Cohort of Individuals With Chronic Low Back Pain","authors":"Carol M. Greco, Nathan E. Dodds, Amanda M. Acevedo, William Anderst, Kevin M. Bell, Jessa Darwin, Anthony Delitto, John M. Jakicic, Gina P. McKernan, Charity G. Patterson, Paul A. Pilkonis, Sara R. Piva, Michael J. Schneider, Nam V. Vo, Ajay D. Wasan, Lan Yu, Gwendolyn A. Sowa","doi":"10.1002/jsp2.70097","DOIUrl":"https://doi.org/10.1002/jsp2.70097","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Chronic low back pain (cLBP) is complex, disabling, and costly to patients and to society. Patients' social circumstances, beliefs, and behaviors interact in a dynamic way with biomedical factors and have the potential to amplify or reduce suffering. It is important to assess the experience of pain via patient-reported outcomes (PROs). The University of Pittsburgh Mechanistic Research Center, entitled, “<i>Low Back Pain: Biological, Biomechanical, Behavioral Phenotypes (LB</i><sup>3</sup><i>P),”</i> is part of the National Institutes of Health's Helping to End Addiction Long-term Initiative. LB<sup>3</sup>P conducted a prospective, observational cohort study to identify phenotypes of over 1000 participants with cLBP. This article reports key information from the PROs and selected demographic variables obtained at the in-person LB<sup>3</sup>P study enrollment visit.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The LB<sup>3</sup>P study participants completed numerous PROs, including the minimum data set assessments of the NIH Research Task Force on back pain and the NIH HEAL Initiative's Common Data Elements. PROs were organized into five conceptual domains: (1) Pain Characteristics and Qualities, (2) Pain-related Psychosocial Factors, (3) General Psychosocial Factors, (4) General Health and Lifestyle Factors, and (5) Social Determinants of Health (SDoH). Patient Acceptance of Symptom Status, which consists of yes/no responses to 10 questions about whether the level of each of the 10 symptoms is satisfactory, was also assessed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>PRO measures were collected from 1007 LB<sup>3</sup>P participants with cLBP. The means and standard deviations, or medians and interquartile ranges, and percentages for the PRO variables collected at the in-person enrollment visit are presented for the overall group and stratified by sex at birth (females and males) and by age (< 60 years old and ≥ 60 years old). For the participants overall, and across sex and age groups, pain intensity and interference were moderate on average. Neuropathic pain, assessed via PainDETECT, was present in 18% of the overall sample, and in 22.5% of those younger than 60. On average, fatigue, depressive and anxiety symptoms, memory and concentration, self-efficacy, and positive outlook were within normal limits, as indicated by PROMIS T-scores. However, PROMIS Physical function was below normal, with T-scores in the mild to moderate range of impairment. When participants were asked to rate the acceptability of their symptom status in 10 areas of function, the most frequently reported areas of dissatisfacti","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70097","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144832815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sara R. Piva, Zakiy Alfikri, William Anderst, Kevin M. Bell, Cristiane Carlesso, Jessa Darwin, Anthony Delitto, Carol M. Greco, Marit E. Johnson, Gina P. McKernan, Rachel McLoughlin, Charity G. Patterson, Rachel E. Roos, Michael J. Schneider, Clair Smith, Gwendolyn A. Sowa, Nam V. Vo, Leming Zhou
<div> <section> <h3> Background</h3> <p>Despite the wide utilization of physical tests and pain assessments to evaluate individuals with chronic low back pain (cLBP), there is limited information about their feasibility in terms of test duration, the ability of individuals with cLBP to perform these tests, and associated adverse events. The literature also lacks reports on comprehensive characterization of physical tests to serve as a reference for clinicians and researchers. The objectives of the present work are to assess the feasibility of a comprehensive battery of physical tests and pain assessments germane to individuals with cLBP and characterize the tests' values in the context of a large cohort.</p> </section> <section> <h3> Methods</h3> <p>This cross-sectional analysis uses enrollment data from a large observational study conducted by the University of Pittsburgh Mechanistic Research Center—“Low Back Pain: Biological, Biomechanical, Behavioral Phenotypes (LB<sup>3</sup>P).” LB<sup>3</sup>P is part of the National Institutes of Health's Helping to End Addiction Long-term Initiative. Individuals with cLBP were screened by trained clinicians who assessed their safety to partake in up to 37 physical tests based on pre-existing medical conditions. Testers could elect not to administer tests based on their clinical judgment and participants could refuse to partake in tests. The reasons for not performing tests were recorded. The feasibility of the tests was assessed by the time to complete each test, percentages and reasons for tests not done, and adverse events related to test performance. Descriptive statistics for the physical tests were computed for the sample overall, and for the subgroups (male/female and age < 60/≥ 60) to serve as reference values for individuals with cLBP.</p> </section> <section> <h3> Results</h3> <p>The testing protocol took on average 130 min. In total, 8.9% of tests were not done. About one third of tests not done were screened out due to medical conditions identified during the safety screening, and two-thirds due to the tester's clinical judgment or participant refusal. Only four adverse events occurred, and they resolved without sequelae. The tests most often omitted were those requiring maximal and submaximal physical effort or could elevate blood pressure in those with hypertension, such as muscle strength testing of the hip, abdomen, and thigh, or hand immersion in cold water. From the 1007 participants enrolled in the study, those who did not complete one or more tests tended to be older, obese, less educated, and experienced more disability and back pain for a longer time. The descriptive statistics of th
{"title":"Feasibility of Physical Exam and Performance-Based Tests in Individuals With Chronic Low Back Pain: A Descriptive Study","authors":"Sara R. Piva, Zakiy Alfikri, William Anderst, Kevin M. Bell, Cristiane Carlesso, Jessa Darwin, Anthony Delitto, Carol M. Greco, Marit E. Johnson, Gina P. McKernan, Rachel McLoughlin, Charity G. Patterson, Rachel E. Roos, Michael J. Schneider, Clair Smith, Gwendolyn A. Sowa, Nam V. Vo, Leming Zhou","doi":"10.1002/jsp2.70096","DOIUrl":"https://doi.org/10.1002/jsp2.70096","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Despite the wide utilization of physical tests and pain assessments to evaluate individuals with chronic low back pain (cLBP), there is limited information about their feasibility in terms of test duration, the ability of individuals with cLBP to perform these tests, and associated adverse events. The literature also lacks reports on comprehensive characterization of physical tests to serve as a reference for clinicians and researchers. The objectives of the present work are to assess the feasibility of a comprehensive battery of physical tests and pain assessments germane to individuals with cLBP and characterize the tests' values in the context of a large cohort.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This cross-sectional analysis uses enrollment data from a large observational study conducted by the University of Pittsburgh Mechanistic Research Center—“Low Back Pain: Biological, Biomechanical, Behavioral Phenotypes (LB<sup>3</sup>P).” LB<sup>3</sup>P is part of the National Institutes of Health's Helping to End Addiction Long-term Initiative. Individuals with cLBP were screened by trained clinicians who assessed their safety to partake in up to 37 physical tests based on pre-existing medical conditions. Testers could elect not to administer tests based on their clinical judgment and participants could refuse to partake in tests. The reasons for not performing tests were recorded. The feasibility of the tests was assessed by the time to complete each test, percentages and reasons for tests not done, and adverse events related to test performance. Descriptive statistics for the physical tests were computed for the sample overall, and for the subgroups (male/female and age < 60/≥ 60) to serve as reference values for individuals with cLBP.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The testing protocol took on average 130 min. In total, 8.9% of tests were not done. About one third of tests not done were screened out due to medical conditions identified during the safety screening, and two-thirds due to the tester's clinical judgment or participant refusal. Only four adverse events occurred, and they resolved without sequelae. The tests most often omitted were those requiring maximal and submaximal physical effort or could elevate blood pressure in those with hypertension, such as muscle strength testing of the hip, abdomen, and thigh, or hand immersion in cold water. From the 1007 participants enrolled in the study, those who did not complete one or more tests tended to be older, obese, less educated, and experienced more disability and back pain for a longer time. The descriptive statistics of th","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70096","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144814982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
We read with interest the article by Xiaoqiang Wang et al. [1] titled “Exploring the Therapeutic Potential of Puerarin on Intervertebral Disc Degeneration by Regulating Apoptosis of Nucleus Pulposus Cells” published in JOR Spine on December 11, 2024. The study presents compelling findings on the role of puerarin in mitigating intervertebral disc degeneration (IDD). However, we would like to raise two critical points regarding the data analysis and interpretation that may affect the validity of the conclusions.
First, in Figure 1E, the intersection size of four different datasets is presented. However, the results appear counterintuitive: the intersection size increases as more datasets are included, while it decreases with fewer datasets. This observation contradicts mathematical principles, as the intersection of multiple datasets typically diminishes with the addition of more datasets due to increased variability and reduced common elements. We suggest that the authors revisit the methodology used to calculate these intersections and verify the data processing steps to ensure accuracy. Clarification on how the intersection sizes were derived would greatly enhance the reliability of this analysis.
Second, the authors did not explicitly state the log2FoldChange threshold used in their differential analysis. Based on Figure 2A, the absolute values appear to range between 0.2 and 0.3. Such a low threshold may result in an overly broad range of differentially expressed genes, potentially reducing the biological significance of the findings [2, 3]. We recommend that the authors justify their choice of threshold and consider applying a more stringent cutoff to improve the robustness of their results. Additionally, exploring the biological relevance of the identified genes through functional enrichment analysis could strengthen the study's conclusions [4].
We believe that addressing these issues would significantly enhance the clarity and impact of the study. We appreciate the authors' contributions to the field and hope that our comments will encourage further refinement of this important work. Thank you for considering our comments. We look forward to the authors' response and any potential follow-up studies.
{"title":"Comments on “Exploring the Therapeutic Potential of Puerarin on Intervertebral Disc Degeneration by Regulating Apoptosis of Nucleus Pulposus Cells”","authors":"Ji Jin, Miao Liu, Jiajie Guo, Hong Sun","doi":"10.1002/jsp2.70099","DOIUrl":"https://doi.org/10.1002/jsp2.70099","url":null,"abstract":"<p>We read with interest the article by Xiaoqiang Wang et al. [<span>1</span>] titled “Exploring the Therapeutic Potential of Puerarin on Intervertebral Disc Degeneration by Regulating Apoptosis of Nucleus Pulposus Cells” published in JOR Spine on December 11, 2024. The study presents compelling findings on the role of puerarin in mitigating intervertebral disc degeneration (IDD). However, we would like to raise two critical points regarding the data analysis and interpretation that may affect the validity of the conclusions.</p><p>First, in Figure 1E, the intersection size of four different datasets is presented. However, the results appear counterintuitive: the intersection size increases as more datasets are included, while it decreases with fewer datasets. This observation contradicts mathematical principles, as the intersection of multiple datasets typically diminishes with the addition of more datasets due to increased variability and reduced common elements. We suggest that the authors revisit the methodology used to calculate these intersections and verify the data processing steps to ensure accuracy. Clarification on how the intersection sizes were derived would greatly enhance the reliability of this analysis.</p><p>Second, the authors did not explicitly state the log2FoldChange threshold used in their differential analysis. Based on Figure 2A, the absolute values appear to range between 0.2 and 0.3. Such a low threshold may result in an overly broad range of differentially expressed genes, potentially reducing the biological significance of the findings [<span>2, 3</span>]. We recommend that the authors justify their choice of threshold and consider applying a more stringent cutoff to improve the robustness of their results. Additionally, exploring the biological relevance of the identified genes through functional enrichment analysis could strengthen the study's conclusions [<span>4</span>].</p><p>We believe that addressing these issues would significantly enhance the clarity and impact of the study. We appreciate the authors' contributions to the field and hope that our comments will encourage further refinement of this important work. Thank you for considering our comments. We look forward to the authors' response and any potential follow-up studies.</p>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70099","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144814983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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