Pub Date : 2024-07-30DOI: 10.1177/19476035241264011
Berardo Di Matteo, Giuseppe Anzillotti, Pietro Conte, Peter Angele, Pieter Emans, Joan Minguell-Monyart, Jennifer Woodell-May, Miguel Correa-Tapia, Elizaveta Kon
Introduction. Bone marrow lesions (BMLs) are MRI-visible subchondral bone alterations, highly correlated with symptoms in the knee. Subchondroplasty (SCP) is able to fill the subchondral defects associated with BMLs using an injectable bone substitute material. The aim of the present study is to evaluate the 12-month outcomes of the SCP in the treatment of symptoms of mild-to-moderate knee osteoarthritis (OA) patients with persistent BMLs of the knee. Materials and Methods. Subjects affected by BMLs of the femoral condyle or tibial plateau that were present for >3 months and not responsive to conservative treatments were enrolled in this prospective multicenter trial. All the patients underwent SCP. Follow-up was conducted at 1, 3, 6 and 12 months. All subjects completed Numerical Rating Scale (NRS) for pain, Knee Injury and Osteoarthritis Outcome (KOOS) score, Euro Quality of life-5 dimensions (EQ-5D) score, and a subject global satisfaction scale. Demographic information of the patients was also collected. Results. A total of 79 patients completed the 12-month follow-up. Statistically significant improvements on all clinical scales were registered from baseline to the 12-month follow-up. No severe adverse events were reported. Four patients were considered failed. A 12-month subgroup analysis was performed to evaluate the possible correlation between all the KOOS subscales and age, gender, number of BMLs, location of BMLs, and Kellgren-Lawrence grade: no statistically significant associations were observed. Conclusion. SCP is a safe and effective procedure for the treatment of symptoms related to persisting BMLs in mild-to-moderate osteoarthritic knees, with a low failure rate up to 12 months' evaluation.
{"title":"Subchondroplasty® (SCP) Provides Resolution of Symptoms and Functional Improvements in Mild-to-Moderate Knee Osteoarthritis with Persistent Bone Marrow Lesions: 12-Month Follow-Up Results from a Multicentric Open-Label Prospective Clinical Trial.","authors":"Berardo Di Matteo, Giuseppe Anzillotti, Pietro Conte, Peter Angele, Pieter Emans, Joan Minguell-Monyart, Jennifer Woodell-May, Miguel Correa-Tapia, Elizaveta Kon","doi":"10.1177/19476035241264011","DOIUrl":"10.1177/19476035241264011","url":null,"abstract":"<p><p><i>Introduction.</i> Bone marrow lesions (BMLs) are MRI-visible subchondral bone alterations, highly correlated with symptoms in the knee. Subchondroplasty (SCP) is able to fill the subchondral defects associated with BMLs using an injectable bone substitute material. The aim of the present study is to evaluate the 12-month outcomes of the SCP in the treatment of symptoms of mild-to-moderate knee osteoarthritis (OA) patients with persistent BMLs of the knee. <i>Materials and Methods.</i> Subjects affected by BMLs of the femoral condyle or tibial plateau that were present for >3 months and not responsive to conservative treatments were enrolled in this prospective multicenter trial. All the patients underwent SCP. Follow-up was conducted at 1, 3, 6 and 12 months. All subjects completed Numerical Rating Scale (NRS) for pain, Knee Injury and Osteoarthritis Outcome (KOOS) score, Euro Quality of life-5 dimensions (EQ-5D) score, and a subject global satisfaction scale. Demographic information of the patients was also collected. <i>Results.</i> A total of 79 patients completed the 12-month follow-up. Statistically significant improvements on all clinical scales were registered from baseline to the 12-month follow-up. No severe adverse events were reported. Four patients were considered failed. A 12-month subgroup analysis was performed to evaluate the possible correlation between all the KOOS subscales and age, gender, number of BMLs, location of BMLs, and Kellgren-Lawrence grade: no statistically significant associations were observed. <i>Conclusion.</i> SCP is a safe and effective procedure for the treatment of symptoms related to persisting BMLs in mild-to-moderate osteoarthritic knees, with a low failure rate up to 12 months' evaluation.</p>","PeriodicalId":9626,"journal":{"name":"CARTILAGE","volume":" ","pages":"19476035241264011"},"PeriodicalIF":2.7,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11569562/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141792043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Objective: To assess articular cartilage degeneration in anterior cruciate ligament (ACL) reconstructed knees as detected by MR T1rho and T2 mapping relative to controls and longitudinally at 3 months and 1 year after ACL reconstruction (ACLR).
Design: Twenty-five patients with acute ACL injury were enrolled (13 women and 12 men; mean age 30.8), and 14 healthy controls were selected by sex and age matching. The affected knees of the ACLR participants were imaged using a 3.0T magnetic resonance (MR) scanner 3 months and 1 year after ACLR. Cartilage T1rho and T2 values were quantified for subcompartments in the full-thickness, superficial, and deep layers and were compared with the matched subcompartments of control knees. The influence of concomitant meniscal tears identified using proton density-weighted imaging (PDWI) was also investigated.
Results: In the posterior lateral tibia, T1rho and T2 values were significantly higher in ACLR participants at 3 months and slightly decreased at 1-year compared to the control group. T1rho values in the medial compartment exhibited a significant increase at 1-year compared with those of control knees, while T2 showed no significance. In cartilage with medial meniscal tears, the T1rho values in multiple medial subcompartments were significantly higher than those in cartilage without medial meniscal tears, and this alteration was relatively detectable by T1rho.
Conclusions: T1rho and T2 mapping is effective in evaluating cartilage degeneration following ACLR. T1rho may exhibit greater sensitivity for assessing the progression of early degeneration in the medial compartment after ACLR.
{"title":"Longitudinal Analysis of Knee Articular Cartilage Degeneration After Anterior Cruciate Ligament Reconstruction: Comparison of T1rho and T2 Mapping.","authors":"Kaoru Toguchi, Atsuya Watanabe, Manato Horii, Shotaro Watanabe, Ryu Itoh, Takuya Sakamoto, Yasuaki Murata, Seiji Ohtori, Takahisa Sasho","doi":"10.1177/19476035241264013","DOIUrl":"10.1177/19476035241264013","url":null,"abstract":"<p><strong>Objective: </strong>To assess articular cartilage degeneration in anterior cruciate ligament (ACL) reconstructed knees as detected by MR T1rho and T2 mapping relative to controls and longitudinally at 3 months and 1 year after ACL reconstruction (ACLR).</p><p><strong>Design: </strong>Twenty-five patients with acute ACL injury were enrolled (13 women and 12 men; mean age 30.8), and 14 healthy controls were selected by sex and age matching. The affected knees of the ACLR participants were imaged using a 3.0T magnetic resonance (MR) scanner 3 months and 1 year after ACLR. Cartilage T1rho and T2 values were quantified for subcompartments in the full-thickness, superficial, and deep layers and were compared with the matched subcompartments of control knees. The influence of concomitant meniscal tears identified using proton density-weighted imaging (PDWI) was also investigated.</p><p><strong>Results: </strong>In the posterior lateral tibia, T1rho and T2 values were significantly higher in ACLR participants at 3 months and slightly decreased at 1-year compared to the control group. T1rho values in the medial compartment exhibited a significant increase at 1-year compared with those of control knees, while T2 showed no significance. In cartilage with medial meniscal tears, the T1rho values in multiple medial subcompartments were significantly higher than those in cartilage without medial meniscal tears, and this alteration was relatively detectable by T1rho.</p><p><strong>Conclusions: </strong>T1rho and T2 mapping is effective in evaluating cartilage degeneration following ACLR. T1rho may exhibit greater sensitivity for assessing the progression of early degeneration in the medial compartment after ACLR.</p>","PeriodicalId":9626,"journal":{"name":"CARTILAGE","volume":" ","pages":"19476035241264013"},"PeriodicalIF":2.7,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11569521/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141757359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Objective: Meniscus progenitor cells (MPCs) have been identified as promising candidates for meniscus regeneration, and it is crucial for us to understand meniscus injury repair mechanism at the cellular level. In this study, we investigate the biological properties of MPCs isolated from different species using the differential adhesion to fibronectin (DAF) technique. We aim to characterize MPCs in different species and evaluate the feasibility of these models for future meniscal investigation.
Design: MPCs were isolated from freshly digested meniscus from rat, rabbit, goat, and human cells using DAF. Biological properties, including proliferation, colony-forming, multilineage differentiation, and migration abilities, were compared in MPCs and their corresponding mixed meniscus cell (MCs) population in each species.
Results: MPCs were successfully isolated by the DAF technique in all species. Rat MPCs appeared cobblestone-like, rabbit MPCs were more polygonal, goat MPCs had a spindle-shaped morphology, human MPCs appear more fibroblast-like. Compared with MCs, isolated MPCs showed progenitor cell characteristics, including multilineage differentiation ability and MSC (mesenchymal stem cells) markers (CD166, CD90, CD44, Stro-1) expression. They also highly expressed fibronectin receptors CD49e and CD49c. MPCs also showed greater proliferation capacity and retained colony-forming ability. Except for goat MPCs showed greater migration abilities than MCs, no significant differences were found in the migration ability between MPCs and MCs in other species.
Conclusion: Our study shows that DAF is an effective method for isolating MPCs from rat, rabbit, goat, and human. MPCs in these species demonstrated similar characteristics, including greater proliferation ability and better chondrogenic potential.
{"title":"Isolation and Characterization of Meniscus Progenitor Cells From Rat, Rabbit, Goat, and Human.","authors":"Wan-Ting Yan, Jing-Song Wang, Shu-Yang Guo, Jia-Hao Zhu, Zheng-Zheng Zhang","doi":"10.1177/19476035241266579","DOIUrl":"10.1177/19476035241266579","url":null,"abstract":"<p><strong>Objective: </strong>Meniscus progenitor cells (MPCs) have been identified as promising candidates for meniscus regeneration, and it is crucial for us to understand meniscus injury repair mechanism at the cellular level. In this study, we investigate the biological properties of MPCs isolated from different species using the differential adhesion to fibronectin (DAF) technique. We aim to characterize MPCs in different species and evaluate the feasibility of these models for future meniscal investigation.</p><p><strong>Design: </strong>MPCs were isolated from freshly digested meniscus from rat, rabbit, goat, and human cells using DAF. Biological properties, including proliferation, colony-forming, multilineage differentiation, and migration abilities, were compared in MPCs and their corresponding mixed meniscus cell (MCs) population in each species.</p><p><strong>Results: </strong>MPCs were successfully isolated by the DAF technique in all species. Rat MPCs appeared cobblestone-like, rabbit MPCs were more polygonal, goat MPCs had a spindle-shaped morphology, human MPCs appear more fibroblast-like. Compared with MCs, isolated MPCs showed progenitor cell characteristics, including multilineage differentiation ability and MSC (mesenchymal stem cells) markers (CD166, CD90, CD44, Stro-1) expression. They also highly expressed fibronectin receptors CD49e and CD49c. MPCs also showed greater proliferation capacity and retained colony-forming ability. Except for goat MPCs showed greater migration abilities than MCs, no significant differences were found in the migration ability between MPCs and MCs in other species.</p><p><strong>Conclusion: </strong>Our study shows that DAF is an effective method for isolating MPCs from rat, rabbit, goat, and human. MPCs in these species demonstrated similar characteristics, including greater proliferation ability and better chondrogenic potential.</p>","PeriodicalId":9626,"journal":{"name":"CARTILAGE","volume":" ","pages":"19476035241266579"},"PeriodicalIF":2.7,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11569696/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141757358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Objective: Mounting evidence suggests that histone deacetylases (HDAC) inhibitors reduce cartilage destruction in animal models of osteoarthritis (OA). Tumor necrosis factor (TNF)-α-blocking treatment for OA may provide effective joint protection by slowing joint damage. To investigate the effects of intraperitoneal administration of etanercept (a TNF-α inhibitor) on OA development in rats and changes in the nociceptive behavior of rats and expression of HDACs, RUNX2, and MMP13 in cartilage.
Methods: Induction of OA in Wistar rats was accomplished through anterior cruciate ligament transection (ACLT). One or five milligrams (mg) of etanercept was administered intraperitoneally for 5 consecutive weeks after ACLT to the ACLT + etanercept (1 and 5 mg/kg) groups. Nociceptive behavior and changes in knee joint width were analyzed. Cartilage was evaluated histologically and immunohistochemically.
Results: ACLT + etanercept significantly improved mechanical allodynia and weight-bearing distribution compared to ACLT alone. In OA rats treated with etanercept, cartilage degeneration and synovitis were significantly less pronounced than those in ACLT rats. OA-affected cartilage also showed reduced expression of HDAC 6, 7, RUNX-2, and MMP-13 in response to etanercept but increased expression of HDAC4.
Conclusion: Our study demonstrated that etanercept therapy (1) attenuated the development of OA and synovitis in rats, (2) reduced nociception, and (3) regulated chondrocyte metabolism, possibly by inhibiting cell HDAC6 and HDAC7, RUNX2, and MMP13 and increasing HDAC4 expression. Based on new evidence, etanercept may have therapeutic potential in OA.
目的:越来越多的证据表明,组蛋白去乙酰化酶(HDAC)抑制剂可减少骨关节炎(OA)动物模型中软骨的破坏。肿瘤坏死因子(TNF)-α阻断剂治疗 OA 可减缓关节损伤,从而有效保护关节。目的:研究腹腔注射依那西普(TNF-α抑制剂)对大鼠OA发生的影响,以及大鼠痛觉行为和软骨中HDACs、RUNX2和MMP13表达的变化:通过前十字韧带横断(ACLT)诱导 Wistar 大鼠发生 OA。前交叉韧带断裂(ACLT)后连续5周腹腔注射1或5毫克依那西普(etanercept),分为ACLT+依那西普(1和5毫克/千克)组。对痛觉行为和膝关节宽度的变化进行了分析。对软骨进行组织学和免疫组化评估:结果:与单用 ACLT 相比,ACLT + etanercept 能明显改善机械异感和负重分布。在接受依那西普治疗的 OA 大鼠中,软骨退化和滑膜炎明显少于 ACLT 大鼠。受OA影响的软骨还显示,HDAC 6、7、RUNX-2和MMP-13的表达对依那西普的反应有所降低,但HDAC4的表达有所增加:我们的研究表明,依那西普治疗(1)减轻了大鼠OA和滑膜炎的发展,(2)减少了痛觉,(3)调节了软骨细胞的新陈代谢,可能是通过抑制细胞HDAC6和HDAC7、RUNX2和MMP13以及增加HDAC4的表达。基于新的证据,etanercept可能具有治疗OA的潜力。
{"title":"Effects of Etanercept on Experimental Osteoarthritis in Rats: Role of Histone Deacetylases.","authors":"Zhi-Hong Wen, Chi-Chieh Tang, Yen-You Lin, Zhi-Kang Yao, Shih-Peng Hsieh, Gar-Hwa-Lai, Wu-Fu Chen, Yen-Hsuan Jean","doi":"10.1177/19476035241264012","DOIUrl":"10.1177/19476035241264012","url":null,"abstract":"<p><strong>Objective: </strong>Mounting evidence suggests that histone deacetylases (HDAC) inhibitors reduce cartilage destruction in animal models of osteoarthritis (OA). Tumor necrosis factor (TNF)-α-blocking treatment for OA may provide effective joint protection by slowing joint damage. To investigate the effects of intraperitoneal administration of etanercept (a TNF-α inhibitor) on OA development in rats and changes in the nociceptive behavior of rats and expression of HDACs, RUNX2, and MMP13 in cartilage.</p><p><strong>Methods: </strong>Induction of OA in Wistar rats was accomplished through anterior cruciate ligament transection (ACLT). One or five milligrams (mg) of etanercept was administered intraperitoneally for 5 consecutive weeks after ACLT to the ACLT + etanercept (1 and 5 mg/kg) groups. Nociceptive behavior and changes in knee joint width were analyzed. Cartilage was evaluated histologically and immunohistochemically.</p><p><strong>Results: </strong>ACLT + etanercept significantly improved mechanical allodynia and weight-bearing distribution compared to ACLT alone. In OA rats treated with etanercept, cartilage degeneration and synovitis were significantly less pronounced than those in ACLT rats. OA-affected cartilage also showed reduced expression of HDAC 6, 7, RUNX-2, and MMP-13 in response to etanercept but increased expression of HDAC4.</p><p><strong>Conclusion: </strong>Our study demonstrated that etanercept therapy (1) attenuated the development of OA and synovitis in rats, (2) reduced nociception, and (3) regulated chondrocyte metabolism, possibly by inhibiting cell HDAC6 and HDAC7, RUNX2, and MMP13 and increasing HDAC4 expression. Based on new evidence, etanercept may have therapeutic potential in OA.</p>","PeriodicalId":9626,"journal":{"name":"CARTILAGE","volume":" ","pages":"19476035241264012"},"PeriodicalIF":2.7,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11569629/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141757357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Objective: Multilineage differentiating stress-enduring (Muse) cells, a pluripotent stem cell subset of mesenchymal stem cells (MSCs), have shown promise for various tissue repairs due to their stress tolerance and multipotent capabilities. We aimed to investigate the differentiation potential in vitro, the dynamics in vivo, and the reparative contribution of Muse cells to osteochondral lesions.
Design: Labeled MSCs were cultured and sorted into Muse and non-Muse (MSCs without Muse cells) groups. These cells were then formed into spheroids, and chondrogenic differentiation was assessed in vitro. Twenty-one immunocompromised mice were used as the in vivo models of osteochondral lesions. Live imaging, macroscopic evaluation, and histological and immunohistochemical analyses were conducted at the 4- and 8-week time points.
Results: Muse cell spheroids were formed, which were larger and stained more intensely with toluidine blue than non-Muse spheroids, indicating better chondrogenic differentiation. Live imaging confirmed luminescence in all 4-week model knees, but only in a few knees at 8 weeks, suggesting cell persistence. Macroscopically and histologically, no significant differences were observed between the Muse and non-Muse groups at 4 and 8 weeks; however, both groups showed better cartilage repair than that of the vehicle group at 8 weeks. No collagen type II generation was observed in the repaired tissues.
Conclusion: The implantation of the spheroids of Muse and non-Muse cells resulted in better healing of osteochondral lesions than that of the controls, and Muse cells had a higher chondrogenic differentiation potential in vitro than non-Muse cells.
{"title":"Investigating the Potential of Multilineage Differentiating Stress-Enduring Cells for Osteochondral Healing.","authors":"Shotaro Watanabe, Hiroaki Hosokawa, Takuya Sakamoto, Manato Horii, Yoshimasa Ono, Seiji Kimura, Satoshi Yamaguchi, Seiji Ohtori, Takahisa Sasho","doi":"10.1177/19476035241262020","DOIUrl":"10.1177/19476035241262020","url":null,"abstract":"<p><strong>Objective: </strong>Multilineage differentiating stress-enduring (Muse) cells, a pluripotent stem cell subset of mesenchymal stem cells (MSCs), have shown promise for various tissue repairs due to their stress tolerance and multipotent capabilities. We aimed to investigate the differentiation potential <i>in vitro</i>, the dynamics <i>in vivo</i>, and the reparative contribution of Muse cells to osteochondral lesions.</p><p><strong>Design: </strong>Labeled MSCs were cultured and sorted into Muse and non-Muse (MSCs without Muse cells) groups. These cells were then formed into spheroids, and chondrogenic differentiation was assessed <i>in vitro</i>. Twenty-one immunocompromised mice were used as the <i>in vivo</i> models of osteochondral lesions. Live imaging, macroscopic evaluation, and histological and immunohistochemical analyses were conducted at the 4- and 8-week time points.</p><p><strong>Results: </strong>Muse cell spheroids were formed, which were larger and stained more intensely with toluidine blue than non-Muse spheroids, indicating better chondrogenic differentiation. Live imaging confirmed luminescence in all 4-week model knees, but only in a few knees at 8 weeks, suggesting cell persistence. Macroscopically and histologically, no significant differences were observed between the Muse and non-Muse groups at 4 and 8 weeks; however, both groups showed better cartilage repair than that of the vehicle group at 8 weeks. No collagen type II generation was observed in the repaired tissues.</p><p><strong>Conclusion: </strong>The implantation of the spheroids of Muse and non-Muse cells resulted in better healing of osteochondral lesions than that of the controls, and Muse cells had a higher chondrogenic differentiation potential <i>in vitro</i> than non-Muse cells.</p>","PeriodicalId":9626,"journal":{"name":"CARTILAGE","volume":" ","pages":"19476035241262020"},"PeriodicalIF":2.7,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11569652/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141417908","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-09DOI: 10.1177/19476035241258170
Jonathan J Bjerre-Bastos, Casper Sejersen, Henning Bay Nielsen, Mikael Boesen, Niels H Secher, Gregorio Distajo, Vincent Flood, Yves Henrotin, Melanie Uebelhoer, Peter Krustrup, Carl-Christian Kitchen, Christian S Thudium, Jeppe R Andersen, Asger R Bihlet
Objective: To investigate how running, cycling, and sedentary cardiovascular stress impact biomarkers of cartilage turnover acutely in subjects with knee osteoarthritis (OA).
Design: This was a sequential, cross-over, clinical study. Forty subjects with primary knee OA underwent moderate-to-high-intensity cycling, running, and adrenaline infusion on separate days. Blood was sampled before, during, and at 6-time points after intervention. On a control day, similar samples were taken. Biomarkers of type II collagen degradation (C2M, T2CM, Coll2-1, Coll2-1NO2), formation (PRO-C2), and aggrecan degradation (ARGS) were measured.
Results: Mean age was 60.4 years, 40% were male, 45% had cumulated Kellgren-Lawrence (KL)-grade (Right + Left knee) of 2 to 3 and 55% had 4 to 6. Analyzing overall changes, area under the curve was significantly lower compared with resting values for ARGS and C2M after cycling and for ARGS after running. Considering individual time points, peak changes in biomarker levels showed reduction in C2M shortly following cycling (T20min = -12.3%, 95% confidence interval [CI]: -19.3% to -5.2%). PRO-C2 increased during cycling (T10min = 14.0%, 95% CI = 4.1% to 23.8%) and running (T20min = 16.5%, 95% CI = 4.3% to 28.6%). T2CM decreased after cycling (T50min = -19.9%, 95% CI = -29.2% to -10.6%), running (T50min = -22.8%, 95% CI = -32.1% to -13.5%), and infusion of adrenaline (peak, T50min = -9.8%, 95% CI = -20.0% to 0.4%). A latent increase was seen in Coll2-1 240 minutes after running (T260min = 21.7%, 95% CI = -1.6% to 45.1%).
Conclusion: Exercise had an impact on cartilage markers, but it did not suggest any detrimental effect on cartilage. Changes following adrenaline infusion suggest a sympathomimetic influence on the serological composition of biomarkers.
{"title":"The Impact of Weight-bearing Exercise, Non-Weight-bearing Exercise, and Cardiovascular Stress on Biochemical Markers of Cartilage Turnover in Patients With Mild to Moderate Knee Osteoarthritis: A Sequential, Cross-Over, Clinical Study.","authors":"Jonathan J Bjerre-Bastos, Casper Sejersen, Henning Bay Nielsen, Mikael Boesen, Niels H Secher, Gregorio Distajo, Vincent Flood, Yves Henrotin, Melanie Uebelhoer, Peter Krustrup, Carl-Christian Kitchen, Christian S Thudium, Jeppe R Andersen, Asger R Bihlet","doi":"10.1177/19476035241258170","DOIUrl":"10.1177/19476035241258170","url":null,"abstract":"<p><strong>Objective: </strong>To investigate how running, cycling, and sedentary cardiovascular stress impact biomarkers of cartilage turnover acutely in subjects with knee osteoarthritis (OA).</p><p><strong>Design: </strong>This was a sequential, cross-over, clinical study. Forty subjects with primary knee OA underwent moderate-to-high-intensity cycling, running, and adrenaline infusion on separate days. Blood was sampled before, during, and at 6-time points after intervention. On a control day, similar samples were taken. Biomarkers of type II collagen degradation (C2M, T2CM, Coll2-1, Coll2-1NO2), formation (PRO-C2), and aggrecan degradation (ARGS) were measured.</p><p><strong>Results: </strong>Mean age was 60.4 years, 40% were male, 45% had cumulated Kellgren-Lawrence (KL)-grade (Right + Left knee) of 2 to 3 and 55% had 4 to 6. Analyzing overall changes, area under the curve was significantly lower compared with resting values for ARGS and C2M after cycling and for ARGS after running. Considering individual time points, peak changes in biomarker levels showed reduction in C2M shortly following cycling (T<sub>20min</sub> = -12.3%, 95% confidence interval [CI]: -19.3% to -5.2%). PRO-C2 increased during cycling (T<sub>10min</sub> = 14.0%, 95% CI = 4.1% to 23.8%) and running (T<sub>20min</sub> = 16.5%, 95% CI = 4.3% to 28.6%). T2CM decreased after cycling (T<sub>50min</sub> = -19.9%, 95% CI = -29.2% to -10.6%), running (T<sub>50min</sub> = -22.8%, 95% CI = -32.1% to -13.5%), and infusion of adrenaline (peak, T<sub>50min</sub> = -9.8%, 95% CI = -20.0% to 0.4%). A latent increase was seen in Coll2-1 240 minutes after running (T<sub>260min</sub> = 21.7%, 95% CI = -1.6% to 45.1%).</p><p><strong>Conclusion: </strong>Exercise had an impact on cartilage markers, but it did not suggest any detrimental effect on cartilage. Changes following adrenaline infusion suggest a sympathomimetic influence on the serological composition of biomarkers.</p>","PeriodicalId":9626,"journal":{"name":"CARTILAGE","volume":" ","pages":"19476035241258170"},"PeriodicalIF":2.7,"publicationDate":"2024-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11569697/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141295600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Objective: Functional polymorphisms of interleukin 16 (IL16) have been reported to be closely related to the risk of osteoarthritis (OA). However, how IL16 affects OA remains unclear. In this study, the role of IL16 in OA and the possible mechanisms were examined.
Methods: We established a meniscal/ligament injury (MLI) post-traumatic OA model in Sprague Dawley rats and an IL1β-induced ADTC5 cells OA model. We detected the expression of IL16, novel-miR-81, MMP3, and MMP13 by quantitative real-time polymerase chain reaction. Western blot was performed to detect the expression of IL16, MMP3, and MMP13. The association between IL16 and novel-miR-81 was confirmed by luciferase reporter assay. Hematoxylin and eosin staining, Safranin O and Fast Green staining, and immunohistochemical staining were performed to clarify the effect of intra-articular injection of novel-miR-81 agomir in rats OA model.
Results: IL16 was upregulated in OA model. Knockdown of IL16 and overexpression of novel-miR-81 downregulated the expression of MMP3 and MMP13. Importantly, IL16 was a key target of novel-miR-81. Intra-articular injection of novel-miR-81 agomir could attenuate OA progression in rats OA model.
Conclusion: Novel-miR-81 targeted IL16 to relieve OA, suggesting that novel-miR-81and IL16 may be new therapeutic targets for OA.
目的:据报道,白细胞介素 16(IL16)的功能多态性与骨关节炎(OA)的发病风险密切相关。然而,IL16 如何影响 OA 仍不清楚。本研究探讨了 IL16 在 OA 中的作用及其可能的机制:方法:我们在 Sprague Dawley 大鼠中建立了半月板/韧带损伤(MLI)后创伤性 OA 模型和 IL1β 诱导的 ADTC5 细胞 OA 模型。我们通过实时定量聚合酶链反应检测了 IL16、novel-miR-81、MMP3 和 MMP13 的表达。通过 Western 印迹检测 IL16、MMP3 和 MMP13 的表达。荧光素酶报告实验证实了 IL16 与新型 miR-81 之间的关联。为了明确在大鼠 OA 模型中关节内注射新型-miR-81 激动剂的效果,还进行了苏木精和伊红染色、沙弗林 O 和快绿染色以及免疫组化染色:结果:IL16在OA模型中上调。结果:IL16 在 OA 模型中上调,敲除 IL16 和过表达 novel-miR-81 会降低 MMP3 和 MMP13 的表达。重要的是,IL16 是 novel-miR-81 的一个关键靶点。在大鼠 OA 模型中,关节内注射新型-miR-81 激动剂可减轻 OA 的进展:结论:novel-miR-81可靶向IL16缓解OA,这表明novel-miR-81和IL16可能是OA的新治疗靶点。
{"title":"IL16 Regulates Osteoarthritis Progression as a Target Gene of Novel-miR-81.","authors":"Ziwei Luo, Qianting Han, Jianghua Lu, Xiyan Ouyang, Yueying Fan, Yangping Liu, Xianxi Zhou, Jiechen Kong, Helu Liu, Aijun Liu, Dongfeng Chen","doi":"10.1177/19476035231168387","DOIUrl":"10.1177/19476035231168387","url":null,"abstract":"<p><strong>Objective: </strong>Functional polymorphisms of interleukin 16 (IL16) have been reported to be closely related to the risk of osteoarthritis (OA). However, how IL16 affects OA remains unclear. In this study, the role of IL16 in OA and the possible mechanisms were examined.</p><p><strong>Methods: </strong>We established a meniscal/ligament injury (MLI) post-traumatic OA model in Sprague Dawley rats and an IL1β-induced ADTC5 cells OA model. We detected the expression of IL16, novel-miR-81, MMP3, and MMP13 by quantitative real-time polymerase chain reaction. Western blot was performed to detect the expression of IL16, MMP3, and MMP13. The association between IL16 and novel-miR-81 was confirmed by luciferase reporter assay. Hematoxylin and eosin staining, Safranin O and Fast Green staining, and immunohistochemical staining were performed to clarify the effect of intra-articular injection of novel-miR-81 agomir in rats OA model.</p><p><strong>Results: </strong>IL16 was upregulated in OA model. Knockdown of IL16 and overexpression of novel-miR-81 downregulated the expression of MMP3 and MMP13. Importantly, IL16 was a key target of novel-miR-81. Intra-articular injection of novel-miR-81 agomir could attenuate OA progression in rats OA model.</p><p><strong>Conclusion: </strong>Novel-miR-81 targeted IL16 to relieve OA, suggesting that novel-miR-81and IL16 may be new therapeutic targets for OA.</p>","PeriodicalId":9626,"journal":{"name":"CARTILAGE","volume":" ","pages":"175-183"},"PeriodicalIF":2.7,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11368893/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9442741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-01Epub Date: 2023-03-29DOI: 10.1177/19476035231164751
Kylie T Callan, Gaston Otarola, Wendy E Brown, Kyriacos A Athanasiou, Dean Wang
Objective: The purpose of this study was to determine the in vitro effects of a single exposure of bupivacaine on the mechanical properties of bovine cartilage explants at 3 weeks.
Design: Femoral condyle articular cartilage explants were aseptically harvested from juvenile bovine stifle joints before being exposed to chondrogenic medium containing 0.50% (wt/vol) bupivacaine, 0.25% (wt/vol) bupivacaine, or no medication (control) for 1 hour. Explants were then washed and maintained in culture in vitro for 3 weeks before testing. Cell viability, tensile and compressive mechanical properties, histological properties, and biochemical properties were then assessed.
Results: Explants exhibited a dose-dependent decrease in mean tensile Young's modulus with increasing bupivacaine concentration (9.86 MPa in the controls, 6.48 MPa in the 0.25% bupivacaine group [P = 0.048], and 4.72 MPa in the 0.50% bupivacaine group [P = 0.005]). Consistent with these results, collagen content and collagen crosslinking decreased with bupivacaine exposure as measured by mass spectrometry. Compressive properties of the explants were unaffected by bupivacaine exposure. Explants also exhibited a trend toward dose-dependent decreases in viability (51.2% for the controls, 47.3% for the 0.25% bupivacaine-exposed group, and 37.0% for the 0.50% bupivacaine-exposed group [P = 0.072]).
Conclusions: Three weeks after 1-hour bupivacaine exposure, the tensile properties of bovine cartilage explants were significantly decreased, while the compressive properties remained unaffected. These decreases in tensile properties corresponded with reductions in collagen content and crosslinking of collagen fibers. Physicians should be judicious regarding the intra-articular administration of bupivacaine in native joints.
{"title":"The Longer-Term Effects of a Single Bupivacaine Exposure on the Mechanical Properties of Native Cartilage Explants.","authors":"Kylie T Callan, Gaston Otarola, Wendy E Brown, Kyriacos A Athanasiou, Dean Wang","doi":"10.1177/19476035231164751","DOIUrl":"10.1177/19476035231164751","url":null,"abstract":"<p><strong>Objective: </strong>The purpose of this study was to determine the <i>in vitro</i> effects of a single exposure of bupivacaine on the mechanical properties of bovine cartilage explants at 3 weeks.</p><p><strong>Design: </strong>Femoral condyle articular cartilage explants were aseptically harvested from juvenile bovine stifle joints before being exposed to chondrogenic medium containing 0.50% (wt/vol) bupivacaine, 0.25% (wt/vol) bupivacaine, or no medication (control) for 1 hour. Explants were then washed and maintained in culture <i>in vitro</i> for 3 weeks before testing. Cell viability, tensile and compressive mechanical properties, histological properties, and biochemical properties were then assessed.</p><p><strong>Results: </strong>Explants exhibited a dose-dependent decrease in mean tensile Young's modulus with increasing bupivacaine concentration (9.86 MPa in the controls, 6.48 MPa in the 0.25% bupivacaine group [<i>P</i> = 0.048], and 4.72 MPa in the 0.50% bupivacaine group [<i>P</i> = 0.005]). Consistent with these results, collagen content and collagen crosslinking decreased with bupivacaine exposure as measured by mass spectrometry. Compressive properties of the explants were unaffected by bupivacaine exposure. Explants also exhibited a trend toward dose-dependent decreases in viability (51.2% for the controls, 47.3% for the 0.25% bupivacaine-exposed group, and 37.0% for the 0.50% bupivacaine-exposed group [<i>P</i> = 0.072]).</p><p><strong>Conclusions: </strong>Three weeks after 1-hour bupivacaine exposure, the tensile properties of bovine cartilage explants were significantly decreased, while the compressive properties remained unaffected. These decreases in tensile properties corresponded with reductions in collagen content and crosslinking of collagen fibers. Physicians should be judicious regarding the intra-articular administration of bupivacaine in native joints.</p>","PeriodicalId":9626,"journal":{"name":"CARTILAGE","volume":" ","pages":"156-163"},"PeriodicalIF":2.7,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11368901/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9557498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Objective: Meniscal tears treated with a partial meniscectomy could induce knee osteoarthritis, thereby altering or damaging knee kinetics and biomechanics. We have developed a meniscal scaffold made of polyglycolic acid (PGA) coated with polylactic acid/caprolactone (PGA scaffold), which could induce new tissue growth of meniscus-like tissue. This study aimed to evaluate the safety and efficacy of a novel meniscal scaffold for the treatment of irreparable meniscal injuries.
Design: This study describes the findings of a cyclic torque test and first clinical trial of a PGA scaffold for inducing meniscus-like tissue in humans. As the first step, biomechanical testing of the PGA scaffold was performed using a cyclic torque test. Six patients underwent arthroscopic implantation of the PGA scaffold. Furthermore, the patients underwent preoperative clinical, serological, radiographic, and magnetic resonance imaging examinations at 3, 6, and 12 months postoperatively. The patients also underwent a second-look arthroscopy 12 months after implantation.
Results: Torque increased with increasing cyclic loading. However, no structural damage to the sample was noted after 70,000 loading cycles. All patients showed improvement in pain, Lysholm scores, Tegner activity scores, International Knee Documentation Committee, and knee injury and osteoarthritis outcome. The second-look arthroscopy revealed that meniscal tissue had regenerated in 5 patients (83%). Radiography and magnetic resonance imaging confirmed no progression of degenerative joint disease.
Conclusions: The PGA scaffold could tolerate shear forces, did not produce safety concerns, and may have therapeutic potentials for irreparable meniscal tears in humans.
{"title":"Safety and Efficacy of a Novel Polyglycolic Acid Meniscal Scaffold for Irreparable Meniscal Tear.","authors":"Shuhei Otsuki, Shunsuke Sezaki, Yoshinori Okamoto, Takashi Ishitani, Hitoshi Wakama, Masashi Neo","doi":"10.1177/19476035231193087","DOIUrl":"10.1177/19476035231193087","url":null,"abstract":"<p><strong>Objective: </strong>Meniscal tears treated with a partial meniscectomy could induce knee osteoarthritis, thereby altering or damaging knee kinetics and biomechanics. We have developed a meniscal scaffold made of polyglycolic acid (PGA) coated with polylactic acid/caprolactone (PGA scaffold), which could induce new tissue growth of meniscus-like tissue. This study aimed to evaluate the safety and efficacy of a novel meniscal scaffold for the treatment of irreparable meniscal injuries.</p><p><strong>Design: </strong>This study describes the findings of a cyclic torque test and first clinical trial of a PGA scaffold for inducing meniscus-like tissue in humans. As the first step, biomechanical testing of the PGA scaffold was performed using a cyclic torque test. Six patients underwent arthroscopic implantation of the PGA scaffold. Furthermore, the patients underwent preoperative clinical, serological, radiographic, and magnetic resonance imaging examinations at 3, 6, and 12 months postoperatively. The patients also underwent a second-look arthroscopy 12 months after implantation.</p><p><strong>Results: </strong>Torque increased with increasing cyclic loading. However, no structural damage to the sample was noted after 70,000 loading cycles. All patients showed improvement in pain, Lysholm scores, Tegner activity scores, International Knee Documentation Committee, and knee injury and osteoarthritis outcome. The second-look arthroscopy revealed that meniscal tissue had regenerated in 5 patients (83%). Radiography and magnetic resonance imaging confirmed no progression of degenerative joint disease.</p><p><strong>Conclusions: </strong>The PGA scaffold could tolerate shear forces, did not produce safety concerns, and may have therapeutic potentials for irreparable meniscal tears in humans.</p>","PeriodicalId":9626,"journal":{"name":"CARTILAGE","volume":" ","pages":"110-119"},"PeriodicalIF":2.7,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11368900/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10073314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-01Epub Date: 2023-09-18DOI: 10.1177/19476035231191202
José M Lamo-Espinosa, Jorge Gómez-Álvarez, Elena Pascual Roquet-Jalmar, Asier Iribarren, Anne Recke, María Cruz Roa, Andrés Valentí-Azcárate, Froilán Granero-Moltó, Mikel San-Julián
Objective: This study was conducted to assess the effect of osteochondroplasty on osteoarthritis (OA) prevention, comparing radiological evolution between identical hips from the same patient who had undergone unilateral surgery.
Design: We retrospectively reviewed radiological evolution between hips with similar shape from the same patient who had undergone unilateral surgery. In all, 56 FAI patients (112 hips) with a mean age of 42.18 ± 9.16 years and had undergone unilateral arthroscopy treatment have been included. Four independent researchers measured Wiberg, Acetabular and Alpha angles, Extrusion index, and Tönnis classification preoperatively to verify that operated and non-operated hips had the same shape. OA evolution was assessed by joint space width (JSW) in 3 different articular points and Tönnis classification.
Results: No preoperative anatomical differences were present between groups (P > 0.05). At the end of follow-up (31.9 months), a decrease of JSW in the 3 points measured was found in OP hips (OP vs. N-OP; P < 0.01). These results were correlated with changes in the proportion of patients who progressed to grade III in Tönnis classification (from 1.3% preoperative to 23.2% at the end of follow-up).
Conclusions: Osteochondroplasty and labrum procedures were not associated with OA prevention. The OP hips showed a faster OA degeneration, which was not seen in the N-OP. These results will encourage hip surgeons to perform further investigations to avoid the "Pandora's Box Opening Process."
{"title":"Femoroacetabular Impingement and the Effect of Osteochondroplasty on Hip Osteoarthritis Prevention: The Pandora's Box Opening Process.","authors":"José M Lamo-Espinosa, Jorge Gómez-Álvarez, Elena Pascual Roquet-Jalmar, Asier Iribarren, Anne Recke, María Cruz Roa, Andrés Valentí-Azcárate, Froilán Granero-Moltó, Mikel San-Julián","doi":"10.1177/19476035231191202","DOIUrl":"10.1177/19476035231191202","url":null,"abstract":"<p><strong>Objective: </strong>This study was conducted to assess the effect of osteochondroplasty on osteoarthritis (OA) prevention, comparing radiological evolution between identical hips from the same patient who had undergone unilateral surgery.</p><p><strong>Design: </strong>We retrospectively reviewed radiological evolution between hips with similar shape from the same patient who had undergone unilateral surgery. In all, 56 FAI patients (112 hips) with a mean age of 42.18 ± 9.16 years and had undergone unilateral arthroscopy treatment have been included. Four independent researchers measured Wiberg, Acetabular and Alpha angles, Extrusion index, and Tönnis classification preoperatively to verify that operated and non-operated hips had the same shape. OA evolution was assessed by joint space width (JSW) in 3 different articular points and Tönnis classification.</p><p><strong>Results: </strong>No preoperative anatomical differences were present between groups (<i>P</i> > 0.05). At the end of follow-up (31.9 months), a decrease of JSW in the 3 points measured was found in OP hips (OP vs. N-OP; <i>P</i> < 0.01). These results were correlated with changes in the proportion of patients who progressed to grade III in Tönnis classification (from 1.3% preoperative to 23.2% at the end of follow-up).</p><p><strong>Conclusions: </strong>Osteochondroplasty and labrum procedures were not associated with OA prevention. The OP hips showed a faster OA degeneration, which was not seen in the N-OP. These results will encourage hip surgeons to perform further investigations to avoid the \"Pandora's Box Opening Process.\"</p>","PeriodicalId":9626,"journal":{"name":"CARTILAGE","volume":" ","pages":"120-129"},"PeriodicalIF":2.7,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11368905/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10313061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}