Xiaolong Chen, Peng Cui, Yongjin Li, Yu Wang, Shibao Lu
Background
Recent studies have provided evidence that structural changes in paraspinal muscles are associated with intervertebral disc degeneration (IDD), ubiquitous with low back pain (LBP), and potentially thought to be regulated by inflammatory processes. However, the links remain unclear.
Objective
The aims of this study were to investigate structural changes in paraspinal muscles that differed in healthy and lumbar disc herniation (LDH) patients, and LDH patients with and without LBP, and to determine the link with the expression of inflammatory marker(s).
Methods
Cross-sectional areas (CSAs) and fatty degeneration of muscles were measured in this prospective cohort study. Multifidus muscle (MM) tissue was procured from included individuals undergoing surgery. Gene expression was quantified using qPCR assays. Independent t-test, Chi-square, and Spearman correlation were used for evaluating the links among structural changes, expression of inflammatory markers, and clinical outcomes.
Results
Functional CSA and fatty degeneration of MM were larger in healthy group than LDH group. A significant increase in fat infiltration in MM in LBP group than in non-LBP group. TNF-alpha (TNF-α) was 28-fold greater in high-fat infiltration group than low-fat infiltration group within MM. Expression of TNF-α and IL-1β in MM was moderately correlated with functional CSA and fatty degeneration of MM, which was moderately correlated with clinical outcomes.
Conclusions
Results support the hypothesis that IDD is associated with dysregulation of inflammatory state of local MM, which provides initial evidence that inflammatory dysregulation in paraspinal muscles has the potential for a broad impact on tissue health and LBP symptoms.
最近的研究证明，脊柱旁肌肉的结构变化与椎间盘退变（IDD）有关，腰背痛（LBP）无处不在，并可能受炎症过程的调节。本研究的目的是调查健康人与腰椎间盘突出症（LDH）患者、有腰背痛与无腰背痛的腰椎间盘突出症患者脊柱旁肌肉的结构变化差异，并确定其与炎症标志物表达之间的联系。这项前瞻性队列研究对肌肉横截面积（CSA）和脂肪变性进行了测量。基因表达采用 qPCR 方法进行量化。采用独立t检验、Chi-square和Spearman相关性来评估结构变化、炎症标志物表达和临床结果之间的联系。与非 LBP 组相比，LBP 组 MM 的脂肪浸润明显增加。在 MM 中，高脂肪浸润组的 TNF-α（TNF-α）是低脂肪浸润组的 28 倍。MM中TNF-α和IL-1β的表达与MM的功能性CSA和脂肪变性呈中度相关，而MM的功能性CSA和脂肪变性与临床结果呈中度相关。研究结果支持了IDD与局部MM炎症状态失调有关的假设，这为脊柱旁肌肉的炎症失调可能对组织健康和LBP症状产生广泛影响提供了初步证据。
{"title":"Links among MRI features in paraspinal muscles, inflammatory processes, and related back pain in patients with lumbar disc herniation","authors":"Xiaolong Chen, Peng Cui, Yongjin Li, Yu Wang, Shibao Lu","doi":"10.1002/jsp2.1310","DOIUrl":"10.1002/jsp2.1310","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Recent studies have provided evidence that structural changes in paraspinal muscles are associated with intervertebral disc degeneration (IDD), ubiquitous with low back pain (LBP), and potentially thought to be regulated by inflammatory processes. However, the links remain unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The aims of this study were to investigate structural changes in paraspinal muscles that differed in healthy and lumbar disc herniation (LDH) patients, and LDH patients with and without LBP, and to determine the link with the expression of inflammatory marker(s).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Cross-sectional areas (CSAs) and fatty degeneration of muscles were measured in this prospective cohort study. Multifidus muscle (MM) tissue was procured from included individuals undergoing surgery. Gene expression was quantified using qPCR assays. Independent <i>t</i>-test, Chi-square, and Spearman correlation were used for evaluating the links among structural changes, expression of inflammatory markers, and clinical outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Functional CSA and fatty degeneration of MM were larger in healthy group than LDH group. A significant increase in fat infiltration in MM in LBP group than in non-LBP group. TNF-alpha (TNF-α) was 28-fold greater in high-fat infiltration group than low-fat infiltration group within MM. Expression of TNF-α and IL-1β in MM was moderately correlated with functional CSA and fatty degeneration of MM, which was moderately correlated with clinical outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Results support the hypothesis that IDD is associated with dysregulation of inflammatory state of local MM, which provides initial evidence that inflammatory dysregulation in paraspinal muscles has the potential for a broad impact on tissue health and LBP symptoms.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"7 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2023-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.1310","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138976924","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}
Hagar M. Kenawy, María I. Nuñez, Xóchitl Morales, Lauren E. Lisiewski, Kevin G. Burt, Min Kyu M. Kim, Leonardo Campos, Nadia Kiridly, Clark T. Hung, Nadeen O. Chahine
Background
Intervertebral disc degeneration (IDD) is a major cause of low back pain (LBP) worldwide. Sexual dimorphism, or sex-based differences, appear to exist in the severity of LBP. However, it is unknown if there are sex-based differences in the inflammatory, biomechanical, biochemical, and histological responses of intervertebral discs (IVDs).
Methods
Caudal (Coccygeal/Co) bone-disc-bone motion segments were isolated from multiple spinal levels (Co8 to Co14) of male and female Sprague–Dawley rats. Changes in motion segment biomechanics and extracellular matrix (ECM) biochemistry (glycosaminoglycan [GAG], collagen [COL], water, and DNA content) were evaluated at baseline and in response to chemical insult (lipopolysaccharide [LPS]) or puncture injury ex vivo. We also investigated the contributions of Toll-like receptor (TLR4) signaling on responses to LPS or puncture injury ex vivo, using a small molecule TLR4 inhibitor, TAK-242.
Results
Findings indicate that IVD motion segments from female donors had greater nitric oxide (NO) release in LPS groups compared to male donors. HMGB1 release was increased in punctured discs, but not LPS injured discs, with no sex effect. Although both male and female discs exhibited reductions in dynamic moduli in response to LPS and puncture injuries, dynamic moduli from female donors were higher than male donors across all groups. In uninjured (baseline) samples, a significant sex effect was observed in nucleus pulposus (NP) DNA and water content. Female annulus fibrosus (AF) also had higher DNA, GAG, and COL content (normalized by dry weight), but lower water content than male AF. Additional injury- and sex-dependent effects were observed in AF GAG/DNA and COL/DNA content. Finally, TAK-242 improved the dynamic modulus of female but not male punctured discs.
Conclusions
Our findings demonstrate that there are differences in rat IVD motion segments based on sex, and that the response to injury in inflammatory, biomechanical, biochemical, and histological outcomes also exhibit sex differences. TLR4 inhibition protected against loss of mechanical integrity of puncture-injured IVD motion segments, with differences responses based on donor sex.
{"title":"Sex differences in the biomechanical and biochemical responses of caudal rat intervertebral discs to injury","authors":"Hagar M. Kenawy, María I. Nuñez, Xóchitl Morales, Lauren E. Lisiewski, Kevin G. Burt, Min Kyu M. Kim, Leonardo Campos, Nadia Kiridly, Clark T. Hung, Nadeen O. Chahine","doi":"10.1002/jsp2.1299","DOIUrl":"10.1002/jsp2.1299","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Intervertebral disc degeneration (IDD) is a major cause of low back pain (LBP) worldwide. Sexual dimorphism, or sex-based differences, appear to exist in the severity of LBP. However, it is unknown if there are sex-based differences in the inflammatory, biomechanical, biochemical, and histological responses of intervertebral discs (IVDs).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Caudal (Coccygeal/Co) bone-disc-bone motion segments were isolated from multiple spinal levels (Co8 to Co14) of male and female Sprague–Dawley rats. Changes in motion segment biomechanics and extracellular matrix (ECM) biochemistry (glycosaminoglycan [GAG], collagen [COL], water, and DNA content) were evaluated at baseline and in response to chemical insult (lipopolysaccharide [LPS]) or puncture injury ex vivo. We also investigated the contributions of Toll-like receptor (TLR4) signaling on responses to LPS or puncture injury ex vivo, using a small molecule TLR4 inhibitor, TAK-242.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Findings indicate that IVD motion segments from female donors had greater nitric oxide (NO) release in LPS groups compared to male donors. HMGB1 release was increased in punctured discs, but not LPS injured discs, with no sex effect. Although both male and female discs exhibited reductions in dynamic moduli in response to LPS and puncture injuries, dynamic moduli from female donors were higher than male donors across all groups. In uninjured (baseline) samples, a significant sex effect was observed in nucleus pulposus (NP) DNA and water content. Female annulus fibrosus (AF) also had higher DNA, GAG, and COL content (normalized by dry weight), but lower water content than male AF. Additional injury- and sex-dependent effects were observed in AF GAG/DNA and COL/DNA content. Finally, TAK-242 improved the dynamic modulus of female but not male punctured discs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our findings demonstrate that there are differences in rat IVD motion segments based on sex, and that the response to injury in inflammatory, biomechanical, biochemical, and histological outcomes also exhibit sex differences. TLR4 inhibition protected against loss of mechanical integrity of puncture-injured IVD motion segments, with differences responses based on donor sex.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"6 4","pages":""},"PeriodicalIF":3.7,"publicationDate":"2023-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.1299","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138586052","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}
Changli Zhang, Madeleine D. Gordon, Katherine M. Joseph, Martha E. Diaz-Hernandez, Hicham Drissi, Svenja Illien-Jünger
Background
Intervertebral disc (IVD) degeneration is associated with chronic back pain. We previously demonstrated that the phosphatase pleckstrin homology domain and leucine-rich repeat protein phosphatase (PHLPP) 1 was positively correlated with IVD degeneration and its deficiency decelerated IVD degeneration in both mouse IVDs and human nucleus pulposus (NP) cells. Small molecule PHLPP inhibitors may offer a translatable method to alleviate IVD degeneration. In this study, we tested the effectiveness of the two PHLPP inhibitors NSC117079 and NSC45586 in promoting a healthy NP phenotype.
Methods
Tail IVDs of 5-month-old wildtype mice were collected and treated with NSC117079 or NSC45586 under low serum conditions ex vivo. Hematoxylin & eosin staining was performed to examine IVD structure and NP cell morphology. The expression of KRT19 was analyzed through immunohistochemistry. Cell apoptosis was assessed by TUNEL assay. Human NP cells were obtained from patients with IVD degeneration. The gene expression of KRT19, ACAN, SOX9, and MMP13 was analyzed via real time qPCR, and AKT phosphorylation and the protein expression of FOXO1 was analyzed via immunoblot.
Results
In a mouse IVD organ culture model, NSC45586, but not NSC117079, preserved vacuolated notochordal cell morphology and KRT19 expression while suppressing cell apoptosis, counteracting the degenerative changes induced by serum deprivation, especially in males. Likewise, in degenerated human NP cells, NSC45586 increased cell viability and the expression of KRT19, ACAN, and SOX9 and reducing the expression of MMP13, while NSC117079 treatment only increased KRT19 expression. Mechanistically, NSC45586 treatment increased FOXO1 protein expression in NP cells, and inhibiting FOXO1 offset NSC45586-induced regenerative potential, especially in males.
Conclusions
Our study indicates that NSC45586 was effective in promoting NP cell health, especially in males, suggesting that PHLPP plays a key role in NP cell homeostasis and that NSC45586 might be a potential drug candidate in treating IVD degeneration.
椎间盘(IVD)退变与慢性背痛有关。我们之前已经证明，磷酸酶pleckstrin同源结构域和富含亮氨酸的重复蛋白磷酸酶(PHLPP) 1与IVD变性呈正相关，并且在小鼠IVD和人髓核(NP)细胞中，它的缺乏减缓了IVD变性。小分子PHLPP抑制剂可能提供一种可翻译的方法来减轻IVD变性。在这项研究中，我们测试了两种PHLPP抑制剂NSC117079和NSC45586在促进健康NP表型方面的有效性。收集5月龄野生型小鼠的尾ivd，在低血清条件下用NSC117079或NSC45586体外处理。苏木精和伊红染色检测IVD结构和NP细胞形态。免疫组化分析KRT19的表达。TUNEL法检测细胞凋亡。从IVD变性患者中获得人NP细胞。real - time qPCR检测KRT19、ACAN、SOX9和MMP13基因表达，免疫印迹检测AKT磷酸化和FOXO1蛋白表达。在小鼠IVD器官培养模型中，NSC45586(而非NSC117079)在抑制细胞凋亡的同时，保留了空泡化脊索细胞形态和KRT19表达，抵消了血清剥夺引起的退行性改变，尤其是在雄性小鼠中。同样，在退化的人NP细胞中，NSC45586增加了细胞活力和KRT19、ACAN和SOX9的表达，降低了MMP13的表达，而NSC117079只增加了KRT19的表达。在机制上，NSC45586处理增加了NP细胞中FOXO1蛋白的表达，抑制FOXO1抵消了NSC45586诱导的再生潜能，尤其是在雄性中。我们的研究表明，NSC45586能有效促进NP细胞健康，特别是在男性中，这表明PHLPP在NP细胞稳态中起关键作用，NSC45586可能是治疗IVD变性的潜在候选药物。
{"title":"Differential efficacy of two small molecule PHLPP inhibitors to promote nucleus Pulposus cell health","authors":"Changli Zhang, Madeleine D. Gordon, Katherine M. Joseph, Martha E. Diaz-Hernandez, Hicham Drissi, Svenja Illien-Jünger","doi":"10.1002/jsp2.1306","DOIUrl":"10.1002/jsp2.1306","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Intervertebral disc (IVD) degeneration is associated with chronic back pain. We previously demonstrated that the phosphatase pleckstrin homology domain and leucine-rich repeat protein phosphatase (PHLPP) 1 was positively correlated with IVD degeneration and its deficiency decelerated IVD degeneration in both mouse IVDs and human nucleus pulposus (NP) cells. Small molecule PHLPP inhibitors may offer a translatable method to alleviate IVD degeneration. In this study, we tested the effectiveness of the two PHLPP inhibitors NSC117079 and NSC45586 in promoting a healthy NP phenotype.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Tail IVDs of 5-month-old wildtype mice were collected and treated with NSC117079 or NSC45586 under low serum conditions ex vivo. Hematoxylin & eosin staining was performed to examine IVD structure and NP cell morphology. The expression of KRT19 was analyzed through immunohistochemistry. Cell apoptosis was assessed by TUNEL assay. Human NP cells were obtained from patients with IVD degeneration. The gene expression of KRT19, ACAN, SOX9, and MMP13 was analyzed via real time qPCR, and AKT phosphorylation and the protein expression of FOXO1 was analyzed via immunoblot.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In a mouse IVD organ culture model, NSC45586, but not NSC117079, preserved vacuolated notochordal cell morphology and KRT19 expression while suppressing cell apoptosis, counteracting the degenerative changes induced by serum deprivation, especially in males. Likewise, in degenerated human NP cells, NSC45586 increased cell viability and the expression of KRT19, ACAN, and SOX9 and reducing the expression of MMP13, while NSC117079 treatment only increased KRT19 expression. Mechanistically, NSC45586 treatment increased FOXO1 protein expression in NP cells, and inhibiting FOXO1 offset NSC45586-induced regenerative potential, especially in males.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our study indicates that NSC45586 was effective in promoting NP cell health, especially in males, suggesting that PHLPP plays a key role in NP cell homeostasis and that NSC45586 might be a potential drug candidate in treating IVD degeneration.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"7 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2023-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.1306","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138602428","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}
Jeffrey L. Hutchinson, Matthew A. Veras, Meghan E. Serjeant, Matthew R. McCann, Ashley L. Kelly, Diana Quinonez, Frank Beier, Cheryle A. Séguin
Background
Intervertebral disc (IVD) degeneration is a major contributor to back pain and disability. The cause of IVD degeneration is multifactorial, with no disease-modifying treatments. Mouse models are commonly used to study IVD degeneration; however, the effects of anatomical location, strain, and sex on the progression of age-associated degeneration are poorly understood.
Methods
A longitudinal study was conducted to characterize age-, anatomical-, and sex-specific differences in IVD degeneration in two commonly used strains of mice, C57BL/6 and CD-1. Histopathological evaluation of the cervical, thoracic, lumbar, and caudal regions of mice at 6, 12, 20, and 24 months of age was conducted by two blinded observers at each IVD for the nucleus pulposus (NP), annulus fibrosus (AF), and the NP/AF boundary compartments, enabling analysis of scores by tissue compartment, summed scores for each IVD, or averaged scores for each anatomical region.
Results
C57BL/6 mice displayed mild IVD degeneration until 24 months of age; at this point, the lumbar spine demonstrated the most degeneration compared to other regions. Degeneration was detected earlier in the CD-1 mice (20 months of age) in both the thoracic and lumbar spine. In CD-1 mice, moderate to severe degeneration was noted in the cervical spine at all time points assessed. In both strains, age-associated IVD degeneration in the thoracic and lumbar spine was associated with increased histopathological scores in all IVD compartments. In both strains, minimal degeneration was detected in caudal IVDs out to 24 months of age. Both C57BL/6 and CD-1 mice displayed sex-specific differences in the presentation and progression of age-associated IVD degeneration.
Conclusions
These results showed that the progression and severity of age-associated degeneration in mouse models is associated with marked differences based on anatomical region, sex, and strain. This information provides a fundamental baseline characterization for users of mouse models to enable effective and appropriate experimental design, interpretation, and comparison between studies.
{"title":"Comparative histopathological analysis of age-associated intervertebral disc degeneration in CD-1 and C57BL/6 mice: Anatomical and sex-based differences","authors":"Jeffrey L. Hutchinson, Matthew A. Veras, Meghan E. Serjeant, Matthew R. McCann, Ashley L. Kelly, Diana Quinonez, Frank Beier, Cheryle A. Séguin","doi":"10.1002/jsp2.1298","DOIUrl":"10.1002/jsp2.1298","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Intervertebral disc (IVD) degeneration is a major contributor to back pain and disability. The cause of IVD degeneration is multifactorial, with no disease-modifying treatments. Mouse models are commonly used to study IVD degeneration; however, the effects of anatomical location, strain, and sex on the progression of age-associated degeneration are poorly understood.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A longitudinal study was conducted to characterize age-, anatomical-, and sex-specific differences in IVD degeneration in two commonly used strains of mice, C57BL/6 and CD-1. Histopathological evaluation of the cervical, thoracic, lumbar, and caudal regions of mice at 6, 12, 20, and 24 months of age was conducted by two blinded observers at each IVD for the nucleus pulposus (NP), annulus fibrosus (AF), and the NP/AF boundary compartments, enabling analysis of scores by tissue compartment, summed scores for each IVD, or averaged scores for each anatomical region.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>C57BL/6 mice displayed mild IVD degeneration until 24 months of age; at this point, the lumbar spine demonstrated the most degeneration compared to other regions. Degeneration was detected earlier in the CD-1 mice (20 months of age) in both the thoracic and lumbar spine. In CD-1 mice, moderate to severe degeneration was noted in the cervical spine at all time points assessed. In both strains, age-associated IVD degeneration in the thoracic and lumbar spine was associated with increased histopathological scores in all IVD compartments. In both strains, minimal degeneration was detected in caudal IVDs out to 24 months of age. Both C57BL/6 and CD-1 mice displayed sex-specific differences in the presentation and progression of age-associated IVD degeneration.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These results showed that the progression and severity of age-associated degeneration in mouse models is associated with marked differences based on anatomical region, sex, and strain. This information provides a fundamental baseline characterization for users of mouse models to enable effective and appropriate experimental design, interpretation, and comparison between studies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"6 4","pages":""},"PeriodicalIF":3.7,"publicationDate":"2023-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.1298","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138605130","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}
Jessica Ornowski, Lucas Dziesinski, Madeline Hess, Roland Krug, Maryse Fortin, Abel Torres-Espin, Sharmila Majumdar, Valentina Pedoia, Noah B. Bonnheim, Jeannie F. Bailey
Background
Paraspinal muscle fat infiltration is associated with spinal degeneration and low back pain, however, quantifying muscle fat using clinical magnetic resonance imaging (MRI) techniques continues to be a challenge. Advanced MRI techniques, including chemical-shift encoding (CSE) based water–fat MRI, enable accurate measurement of muscle fat, but such techniques are not widely available in routine clinical practice.
Methods
To facilitate assessment of paraspinal muscle fat using clinical imaging, we compared four thresholding approaches for estimating muscle fat fraction (FF) using T1- and T2-weighted images, with measurements from water–fat MRI as the ground truth: Gaussian thresholding, Otsu's method, K-mean clustering, and quadratic discriminant analysis. Pearson's correlation coefficients (r), mean absolute errors, and mean bias errors were calculated for FF estimates from T1- and T2-weighted MRI with water–fat MRI for the lumbar multifidus (MF), erector spinae (ES), quadratus lumborum (QL), and psoas (PS), and for all muscles combined.
Results
We found that for all muscles combined, FF measurements from T1- and T2-weighted images were strongly positively correlated with measurements from the water–fat images for all thresholding techniques (r = 0.70–0.86, p < 0.0001) and that variations in inter-muscle correlation strength were much greater than variations in inter-method correlation strength.
Conclusion
We conclude that muscle FF can be quantified using thresholded T1- and T2-weighted MRI images with relatively low bias and absolute error in relation to water–fat MRI, particularly in the MF and ES, and the choice of thresholding technique should depend on the muscle and clinical MRI sequence of interest.
棘旁肌肉脂肪浸润与脊柱退变和腰痛有关，然而，使用临床磁共振成像(MRI)技术量化肌肉脂肪仍然是一个挑战。先进的MRI技术，包括基于化学移位编码(CSE)的水脂肪MRI，可以精确测量肌肉脂肪，但这些技术在常规临床实践中并不广泛使用。为了便于临床影像学评估棘旁肌脂肪，我们比较了使用T1和T2加权图像估计肌肉脂肪分数(FF)的四种阈值方法，并将水脂肪MRI测量结果作为基本事实:高斯阈值法、Otsu方法、K均值聚类和二次判别分析。用水脂肪MRI对腰多裂肌(MF)、竖脊肌(ES)、腰方肌(QL)和腰肌(PS)以及所有肌肉进行T1 -和T2 -加权MRI的FF估计，计算Pearson相关系数(r)、平均绝对误差和平均偏倚误差。我们发现，对于所有肌肉，T1和T2加权图像的FF测量值与所有阈值技术的水-脂肪图像测量值呈强正相关(r = 0.70-0.86, p < 0.0001)，肌肉间相关强度的变化远远大于方法间相关强度的变化。我们得出结论，肌肉FF可以使用阈值T1和T2加权MRI图像进行量化，相对于水脂肪MRI，特别是MF和ES，其偏差和绝对误差相对较低，阈值技术的选择应取决于感兴趣的肌肉和临床MRI序列。
{"title":"Thresholding approaches for estimating paraspinal muscle fat infiltration using T1- and T2-weighted MRI: Comparative analysis using water–fat MRI","authors":"Jessica Ornowski, Lucas Dziesinski, Madeline Hess, Roland Krug, Maryse Fortin, Abel Torres-Espin, Sharmila Majumdar, Valentina Pedoia, Noah B. Bonnheim, Jeannie F. Bailey","doi":"10.1002/jsp2.1301","DOIUrl":"10.1002/jsp2.1301","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Paraspinal muscle fat infiltration is associated with spinal degeneration and low back pain, however, quantifying muscle fat using clinical magnetic resonance imaging (MRI) techniques continues to be a challenge. Advanced MRI techniques, including chemical-shift encoding (CSE) based water–fat MRI, enable accurate measurement of muscle fat, but such techniques are not widely available in routine clinical practice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>To facilitate assessment of paraspinal muscle fat using clinical imaging, we compared four thresholding approaches for estimating muscle fat fraction (FF) using T1- and T2-weighted images, with measurements from water–fat MRI as the ground truth: Gaussian thresholding, Otsu's method, K-mean clustering, and quadratic discriminant analysis. Pearson's correlation coefficients (<i>r</i>), mean absolute errors, and mean bias errors were calculated for FF estimates from T1- and T2-weighted MRI with water–fat MRI for the lumbar multifidus (MF), erector spinae (ES), quadratus lumborum (QL), and psoas (PS), and for all muscles combined.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We found that for all muscles combined, FF measurements from T1- and T2-weighted images were strongly positively correlated with measurements from the water–fat images for all thresholding techniques (<i>r =</i> 0.70–0.86, <i>p <</i> 0.0001) and that variations in inter-muscle correlation strength were much greater than variations in inter-method correlation strength.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>We conclude that muscle FF can be quantified using thresholded T1- and T2-weighted MRI images with relatively low bias and absolute error in relation to water–fat MRI, particularly in the MF and ES, and the choice of thresholding technique should depend on the muscle and clinical MRI sequence of interest.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"7 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.1301","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138620759","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}
Christopher J. Panebianco, Caroline Constant, Andrea J. Vernengo, Dirk Nehrbass, Dominic Gehweiler, Tyler J. DiStefano, Jesse Martin, David J. Alpert, Saad B. Chaudhary, Andrew C. Hecht, Alan C. Seifert, Steven B. Nicoll, Sibylle Grad, Stephan Zeiter, James C. Iatridis
Background
Intervertebral disc (IVD) disorders (e.g., herniation) directly contribute to back pain, which is a leading cause of global disability. Next-generation treatments for IVD herniation need advanced preclinical testing to evaluate their ability to repair large defects, prevent reherniation, and limit progressive degeneration. This study tested whether experimental, injectable, and nonbioactive biomaterials could slow IVD degeneration in an ovine discectomy model.
Methods
Ten skeletally mature sheep (4–5.5 years) experienced partial discectomy injury with cruciate-style annulus fibrosus (AF) defects and 0.1 g nucleus pulposus (NP) removal in the L1–L2, L2–L3, and L3–L4 lumbar IVDs. L4–L5 IVDs were Intact controls. IVD injury levels received: (1) no treatment (Injury), (2) poly (ethylene glycol) diacrylate (PEGDA), (3) genipin-crosslinked fibrin (FibGen), (4) carboxymethylcellulose–methylcellulose (C-MC), or (5) C-MC and FibGen (FibGen + C-MC). Animals healed for 12 weeks, then IVDs were assessed using computed tomography (CT), magnetic resonance (MR) imaging, and histopathology.
Results
All repaired IVDs retained ~90% of their preoperative disc height and showed minor degenerative changes by Pfirrmann grading. All repairs had similar disc height loss and Pfirrmann grade as Injury IVDs. Adhesive AF sealants (i.e., PEGDA and FibGen) did not herniate, although repair caused local endplate (EP) changes and inflammation. NP repair biomaterials (i.e., C-MC) and combination repair (i.e., FibGen + C-MC) exhibited lower levels of degeneration, less EP damage, and less severe inflammation; however, C-MC showed signs of herniation via biomaterial expulsion.
Conclusions
All repair IVDs were noninferior to Injury IVDs by IVD height loss and Pfirrmann grade. C-MC and FibGen + C-MC IVDs had the best outcomes, and may be appropriate for enhancement with bioactive factors (e.g., cells, growth factors, and miRNAs). Such bioactive factors appear to be necessary to prevent injury-induced IVD degeneration. Application of AF sealants alone (i.e., PEGDA and FibGen) resulted in EP damage and inflammation, particularly for PEGDA IVDs, suggesting further material refinements are needed.
{"title":"Combining adhesive and nonadhesive injectable hydrogels for intervertebral disc repair in an ovine discectomy model","authors":"Christopher J. Panebianco, Caroline Constant, Andrea J. Vernengo, Dirk Nehrbass, Dominic Gehweiler, Tyler J. DiStefano, Jesse Martin, David J. Alpert, Saad B. Chaudhary, Andrew C. Hecht, Alan C. Seifert, Steven B. Nicoll, Sibylle Grad, Stephan Zeiter, James C. Iatridis","doi":"10.1002/jsp2.1293","DOIUrl":"10.1002/jsp2.1293","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Intervertebral disc (IVD) disorders (e.g., herniation) directly contribute to back pain, which is a leading cause of global disability. Next-generation treatments for IVD herniation need advanced preclinical testing to evaluate their ability to repair large defects, prevent reherniation, and limit progressive degeneration. This study tested whether experimental, injectable, and nonbioactive biomaterials could slow IVD degeneration in an ovine discectomy model.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Ten skeletally mature sheep (4–5.5 years) experienced partial discectomy injury with cruciate-style annulus fibrosus (AF) defects and 0.1 g nucleus pulposus (NP) removal in the L1–L2, L2–L3, and L3–L4 lumbar IVDs. L4–L5 IVDs were Intact controls. IVD injury levels received: (1) no treatment (Injury), (2) poly (ethylene glycol) diacrylate (PEGDA), (3) genipin-crosslinked fibrin (FibGen), (4) carboxymethylcellulose–methylcellulose (C-MC), or (5) C-MC and FibGen (FibGen + C-MC). Animals healed for 12 weeks, then IVDs were assessed using computed tomography (CT), magnetic resonance (MR) imaging, and histopathology.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>All repaired IVDs retained ~90% of their preoperative disc height and showed minor degenerative changes by Pfirrmann grading. All repairs had similar disc height loss and Pfirrmann grade as Injury IVDs. Adhesive AF sealants (i.e., PEGDA and FibGen) did not herniate, although repair caused local endplate (EP) changes and inflammation. NP repair biomaterials (i.e., C-MC) and combination repair (i.e., FibGen + C-MC) exhibited lower levels of degeneration, less EP damage, and less severe inflammation; however, C-MC showed signs of herniation via biomaterial expulsion.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>All repair IVDs were noninferior to Injury IVDs by IVD height loss and Pfirrmann grade. C-MC and FibGen + C-MC IVDs had the best outcomes, and may be appropriate for enhancement with bioactive factors (e.g., cells, growth factors, and miRNAs). Such bioactive factors appear to be necessary to prevent injury-induced IVD degeneration. Application of AF sealants alone (i.e., PEGDA and FibGen) resulted in EP damage and inflammation, particularly for PEGDA IVDs, suggesting further material refinements are needed.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"6 4","pages":""},"PeriodicalIF":3.7,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.1293","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138612214","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}
Jeffrey C. Lotz, Glen Ropella, Paul Anderson, Qian Yang, Michael A. Hedderich, Jeannie Bailey, C. Anthony Hunt
Chronic low back pain (LBP) is influenced by a broad spectrum of patient-specific factors as codified in domains of the biopsychosocial model (BSM). Operationalizing the BSM into research and clinical care is challenging because most investigators work in silos that concentrate on only one or two BSM domains. Furthermore, the expanding, multidisciplinary nature of BSM research creates practical limitations as to how individual investigators integrate current data into their processes of generating impactful hypotheses. The rapidly advancing field of artificial intelligence (AI) is providing new tools for organizing knowledge, but the practical aspects for how AI may advance LBP research and clinical are beginning to be explored. The goals of the work presented here are to: (1) explore the current capabilities of knowledge integration technologies (large language models (LLM), similarity graphs (SGs), and knowledge graphs (KGs)) to synthesize biomedical literature and depict multimodal relationships reflected in the BSM, and; (2) highlight limitations, implementation details, and future areas of research to improve performance. We demonstrate preliminary evidence that LLMs, like GPT-3, may be useful in helping scientists analyze and distinguish cLBP publications across multiple BSM domains and determine the degree to which the literature supports or contradicts emergent hypotheses. We show that SG representations and KGs enable exploring LBP's literature in novel ways, possibly providing, trans-disciplinary perspectives or insights that are currently difficult, if not infeasible to achieve. The SG approach is automated, simple, and inexpensive to execute, and thereby may be useful for early-phase literature and narrative explorations beyond one's areas of expertise. Likewise, we show that KGs can be constructed using automated pipelines, queried to provide semantic information, and analyzed to explore trans-domain linkages. The examples presented support the feasibility for LBP-tailored AI protocols to organize knowledge and support developing and refining trans-domain hypotheses.
{"title":"An exploration of knowledge-organizing technologies to advance transdisciplinary back pain research","authors":"Jeffrey C. Lotz, Glen Ropella, Paul Anderson, Qian Yang, Michael A. Hedderich, Jeannie Bailey, C. Anthony Hunt","doi":"10.1002/jsp2.1300","DOIUrl":"https://doi.org/10.1002/jsp2.1300","url":null,"abstract":"<p>Chronic low back pain (LBP) is influenced by a broad spectrum of patient-specific factors as codified in domains of the biopsychosocial model (BSM). Operationalizing the BSM into research and clinical care is challenging because most investigators work in silos that concentrate on only one or two BSM domains. Furthermore, the expanding, multidisciplinary nature of BSM research creates practical limitations as to how individual investigators integrate current data into their processes of generating impactful hypotheses. The rapidly advancing field of artificial intelligence (AI) is providing new tools for organizing knowledge, but the practical aspects for how AI may advance LBP research and clinical are beginning to be explored. The goals of the work presented here are to: (1) explore the current capabilities of knowledge integration technologies (large language models (LLM), similarity graphs (SGs), and knowledge graphs (KGs)) to synthesize biomedical literature and depict multimodal relationships reflected in the BSM, and; (2) highlight limitations, implementation details, and future areas of research to improve performance. We demonstrate preliminary evidence that LLMs, like GPT-3, may be useful in helping scientists analyze and distinguish cLBP publications across multiple BSM domains and determine the degree to which the literature supports or contradicts emergent hypotheses. We show that SG representations and KGs enable exploring LBP's literature in novel ways, possibly providing, trans-disciplinary perspectives or insights that are currently difficult, if not infeasible to achieve. The SG approach is automated, simple, and inexpensive to execute, and thereby may be useful for early-phase literature and narrative explorations beyond one's areas of expertise. Likewise, we show that KGs can be constructed using automated pipelines, queried to provide semantic information, and analyzed to explore trans-domain linkages. The examples presented support the feasibility for LBP-tailored AI protocols to organize knowledge and support developing and refining trans-domain hypotheses.</p>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"6 4","pages":""},"PeriodicalIF":3.7,"publicationDate":"2023-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.1300","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139047616","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}
Juyi Li, Xiaofang Liang, Xiufang Wang, Pei Yang, Xiaofei Jian, Lei Fu, Aiping Deng, Chao Liu, Jianxin Liu
Objective
This study aimed to identify the molecular defects and clinical manifestations in a Chinese family with brachydactyly (BD) type A1 (BDA1) and multiple-synostoses syndrome 2 (SYNS2).
Methods
A Chinese family with BDA1 and SYNS2 was enrolled in this study. Whole-exome sequencing was used to analyze the gene variants in the proband. The sequences of the candidate pathogenic variant in GDF5 was validated via Sanger sequencing. I-TASSER and PyMOL were used to analyze the functional domains of the corresponding mutant proteins.
Results
The family was found to have an autosomal-dominantly inherited combination of BDA1 and SYNS2 caused by the S475N variant in the GDF5 gene. The variant was located within the functional region, and the mutated residue was found to be highly conserved among species. Via bioinformatic analyses, we predicted this variant to be deleterious, which perturb the protein function. The substitution of the negatively charged amino acid S475 with the neutral N475 was predicted to disrupt the formation of salt bridges with Y487 and impair the structure, stability, and function of the protein, consequently, the abnormalities in cartilage and bone development ensue.
Conclusions
A single genetic variant (S475N) which disrupt the formation of salt bridges with Y487, in the interface of the antagonist- and receptor-binding sites of GDF5 concurrently causes two pathological mechanisms. This is the first report of this variant, identified in a Chinese family with BDA1 and SYNS2.
{"title":"A missense GDF5 variant causes brachydactyly type A1 and multiple-synostoses syndrome 2","authors":"Juyi Li, Xiaofang Liang, Xiufang Wang, Pei Yang, Xiaofei Jian, Lei Fu, Aiping Deng, Chao Liu, Jianxin Liu","doi":"10.1002/jsp2.1302","DOIUrl":"10.1002/jsp2.1302","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This study aimed to identify the molecular defects and clinical manifestations in a Chinese family with brachydactyly (BD) type A1 (BDA1) and multiple-synostoses syndrome 2 (SYNS2).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A Chinese family with BDA1 and SYNS2 was enrolled in this study. Whole-exome sequencing was used to analyze the gene variants in the proband. The sequences of the candidate pathogenic variant in <i>GDF5</i> was validated via Sanger sequencing. I-TASSER and PyMOL were used to analyze the functional domains of the corresponding mutant proteins.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The family was found to have an autosomal-dominantly inherited combination of BDA1 and SYNS2 caused by the S475N variant in the <i>GDF5</i> gene. The variant was located within the functional region, and the mutated residue was found to be highly conserved among species. Via bioinformatic analyses, we predicted this variant to be deleterious, which perturb the protein function. The substitution of the negatively charged amino acid S475 with the neutral N475 was predicted to disrupt the formation of salt bridges with Y487 and impair the structure, stability, and function of the protein, consequently, the abnormalities in cartilage and bone development ensue.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>A single genetic variant (S475N) which disrupt the formation of salt bridges with Y487, in the interface of the antagonist- and receptor-binding sites of GDF5 concurrently causes two pathological mechanisms. This is the first report of this variant, identified in a Chinese family with BDA1 and SYNS2.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"7 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2023-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.1302","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139223573","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}
Thomas Bitterli, David Schmid, Ladina Ettinger, Olga Krupkova, Frances C. Bach, Marianna A. Tryfonidou, Björn P. Meij, Antonio Pozzi, Frank Steffen, Karin Wuertz-Kozak, Lucas A. Smolders
Background
The regulation of inflammatory mediators in the degenerating intervertebral disc (IVD) and corresponding ligamentum flavum (LF) is a topic of emerging interest. The study aimed to investigate the expression of a broad array of inflammatory mediators in the degenerated LF and IVD using a dog model of spontaneous degenerative disc disease (DDD) to determine potential treatment targets.
Methods
LF and IVD tissues were collected from 22 normal dogs (Pfirrmann grades I and II) and 18 dogs affected by DDD (Pfirrmann grades III and IV). A qPCR gene array was used to investigate the expression of 80 inflammatory genes for LF and IVD tissues, whereafter targets of interest were investigated in additional tissue samples using qPCR, western blot (WB), and immunohistochemistry.
Results
Tumor necrosis factor superfamily (TNFSF) signaling was identified as a regulated pathway in DDD, based on the significant regulation (n-fold ± SD) of various TNFSF members in the degenerated IVD, including nerve growth factor (NGF; −8 ± 10), CD40LG (464 ± 442), CD70 (341 ± 336), TNFSF Ligand 10 (9 ± 8), and RANKL/TNFSF Ligand 11 (85 ± 74). In contrast, TNFSF genes were not significantly affected in the degenerated LF compared to the control LF. Protein expression of NGF (WB) was significantly upregulated in both the degenerated LF (4.4 ± 0.5) and IVD (11.3 ± 5.6) compared to the control group. RANKL immunopositivity was significantly upregulated in advanced stages of degeneration (Thompson grades IV and V) in the nucleus pulposus and annulus fibrosus of the IVD, but not in the LF.
Conclusions
DDD involves a significant upregulation of various TNFSF members, with tissue-specific expression profiles in LF and IVD tissues. The differential involvement of TNFSF members within multiple spinal tissues from the same individual provides new insights into the inflammatory processes involved in DDD and may provide a basis to formulate hypotheses for the determination of potential treatment targets.
{"title":"Targeted screening of inflammatory mediators in spontaneous degenerative disc disease in dogs reveals an upregulation of the tumor necrosis superfamily","authors":"Thomas Bitterli, David Schmid, Ladina Ettinger, Olga Krupkova, Frances C. Bach, Marianna A. Tryfonidou, Björn P. Meij, Antonio Pozzi, Frank Steffen, Karin Wuertz-Kozak, Lucas A. Smolders","doi":"10.1002/jsp2.1292","DOIUrl":"10.1002/jsp2.1292","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The regulation of inflammatory mediators in the degenerating intervertebral disc (IVD) and corresponding ligamentum flavum (LF) is a topic of emerging interest. The study aimed to investigate the expression of a broad array of inflammatory mediators in the degenerated LF and IVD using a dog model of spontaneous degenerative disc disease (DDD) to determine potential treatment targets.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>LF and IVD tissues were collected from 22 normal dogs (Pfirrmann grades I and II) and 18 dogs affected by DDD (Pfirrmann grades III and IV). A qPCR gene array was used to investigate the expression of 80 inflammatory genes for LF and IVD tissues, whereafter targets of interest were investigated in additional tissue samples using qPCR, western blot (WB), and immunohistochemistry.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Tumor necrosis factor superfamily (TNFSF) signaling was identified as a regulated pathway in DDD, based on the significant regulation (<i>n</i>-fold ± SD) of various TNFSF members in the degenerated IVD, including <i>nerve growth factor</i> (<i>NGF</i>; −8 ± 10), <i>CD40LG</i> (464 ± 442), <i>CD70</i> (341 ± 336), <i>TNFSF Ligand 10</i> (9 ± 8), and <i>RANKL/TNFSF Ligand 11</i> (85 ± 74). In contrast, TNFSF genes were not significantly affected in the degenerated LF compared to the control LF. Protein expression of NGF (WB) was significantly upregulated in both the degenerated LF (4.4 ± 0.5) and IVD (11.3 ± 5.6) compared to the control group. RANKL immunopositivity was significantly upregulated in advanced stages of degeneration (Thompson grades IV and V) in the nucleus pulposus and annulus fibrosus of the IVD, but not in the LF.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>DDD involves a significant upregulation of various TNFSF members, with tissue-specific expression profiles in LF and IVD tissues. The differential involvement of TNFSF members within multiple spinal tissues from the same individual provides new insights into the inflammatory processes involved in DDD and may provide a basis to formulate hypotheses for the determination of potential treatment targets.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"7 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2023-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.1292","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139242816","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}
Lachlan J. Smith, John T. Martin, Makarand V. Risbud
The sixth biennial ORS PSRS International Spine Research Symposium was held from November 6 to 10, 2022, at Skytop Lodge in northeastern Pennsylvania, USA. Organized jointly by the Orthopaedic Research Society and the Philadelphia Spine Research Society, the symposium attracted more than 200 participants from 15 different countries who came together to share the latest advances in basic and preclinical spine research. Following the symposium, selected participants were invited to submit full-length manuscripts to this special issue of JOR Spine.
{"title":"Advancing basic and preclinical spine research: Highlights from the ORS PSRS 6th International Spine Research Symposium","authors":"Lachlan J. Smith, John T. Martin, Makarand V. Risbud","doi":"10.1002/jsp2.1308","DOIUrl":"https://doi.org/10.1002/jsp2.1308","url":null,"abstract":"<p>The sixth biennial ORS PSRS International Spine Research Symposium was held from November 6 to 10, 2022, at Skytop Lodge in northeastern Pennsylvania, USA. Organized jointly by the Orthopaedic Research Society and the Philadelphia Spine Research Society, the symposium attracted more than 200 participants from 15 different countries who came together to share the latest advances in basic and preclinical spine research. Following the symposium, selected participants were invited to submit full-length manuscripts to this special issue of <i>JOR Spine</i>.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"6 4","pages":""},"PeriodicalIF":3.7,"publicationDate":"2023-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.1308","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139042038","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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