CARTILAGEPub Date : 2024-04-20DOI: 10.1177/19476035241245803
Yu Jung Kim, Jin Han, Seungwoo Han
{"title":"The Interplay Between Endoplasmic Reticulum Stress and Oxidative Stress in Chondrocyte Catabolism","authors":"Yu Jung Kim, Jin Han, Seungwoo Han","doi":"10.1177/19476035241245803","DOIUrl":"https://doi.org/10.1177/19476035241245803","url":null,"abstract":"ObjectiveOxidative stress and endoplasmic reticulum (ER) stress play pivotal roles in disrupting the homeostasis of chondrocytes by producing catalytic proteases and enhancing chondrocyte senescence, consequently contributing to the progression of osteoarthritis (OA). Despite their close interaction, the underlying molecular mechanisms remain poorly understood. Here, we show that ER stress and oxidative stress reciprocally modulate each other to promote cartilage degradation.MethodsPrimary chondrocytes were obtained from the articular cartilage of 5-day-old C57BL/6J mice by excising distal femur and proximal tibia. Tunicamycin was applied to induce ER stress in primary chondrocytes. Surgical OA was induced in 12-week-old male C57BL/6J mice by destabilizing the medial meniscus (DMM).ResultsTunicamycin-induced ER stress led to an increase in the production of reactive oxygen species (ROS) and catalytic proteases, including MMP13 and Adamts5, in primary chondrocytes, and it was primarily dependent on the NADPH oxidase (NOX) system. ER stress directly increased the expression of NOX2, NOX3, NOX4, and p22phox. Specifically, the protein kinase RNA-like ER kinase (PERK) pathway is involved in the expression of NOX4 and p22phox, the inositol-requiring enzyme 1 alpha (IRE1α) pathway in NOX2 and NOX3 expression, and the activating transcription factor 6 (ATF6) pathway influences NOX3 expression in chondrocytes. Conversely, inhibiting NOX function significantly reduced both ER stress sensor–related signaling and chondrocyte catabolism, thereby decelerating the progression of surgically induced OA in vivo.ConclusionsOur findings highlight the positive feedback loop between ER stress and oxidative stress in OA pathogenesis, suggesting that targeting NOX isoforms is a promising therapeutic strategy for OA.","PeriodicalId":9626,"journal":{"name":"CARTILAGE","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140628479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"BMSC-Derived Exosomes Attenuate Rat Osteoarthritis by Regulating Macrophage Polarization through PINK1/Parkin Signaling Pathway","authors":"Beibei Li, Enpu Shen, Zhiwen Wu, Hui Qi, Cheng’ai Wu, Danping Liu, Xu Jiang","doi":"10.1177/19476035241245805","DOIUrl":"https://doi.org/10.1177/19476035241245805","url":null,"abstract":"ObjectiveExosomes derived from bone marrow mesenchymal stem cells (BMSC-Exos) may modulate the M1/M2 polarization of macrophages during osteoarthritis (OA). However, the underlying mechanisms of BMSC-Exos in this process still need to be elucidated. In this study, we explored the role of BMSC-Exos in the polarization of macrophages in vitro and the OA rats in vivo.MethodsThe effects of BMSC-Exos on RAW264.7 cells were determined, including the production of reactive oxygen species (ROS) and the protein expression of Akt, PINK1, and Parkin. We prepared an OA model by resecting the anterior cruciate ligament and medial meniscus of Sprague–Dawley (SD) rats. Hematoxylin-eosin (H&E) and safranin O-fast green staining, immunohistochemistry and immunofluorescence analyses, and the examination of interleukin 6 (IL-6), interleukin 1β (IL-1β), tumor necrosis factor alpha (TNF-α), and interleukin 10 (IL-10) were performed to assess changes in cartilage and synovium.ResultsBMSC-Exos inhibited mitochondrial membrane damage, ROS production, and the protein expression of PINK1 and Parkin. Akt phosphorylation was downregulated under lipopolysaccharide (LPS) induction but significantly recovered after treatment with BMSC-Exos. BMSC-Exos alleviated cartilage damage, inhibited M1 polarization, and promoted M2 polarization in the synovium in OA rats. The expression of PINK1 and Parkin in the synovium and the levels of IL-6, IL-1β, and TNF-α in the serum decreased, but the level of IL-10 increased when BMSC-Exos were used in OA rats.ConclusionBMSC-Exos ameliorate OA development by regulating synovial macrophage polarization, and one of the underlying mechanisms may be through inhibiting PINK1/Parkin signaling.","PeriodicalId":9626,"journal":{"name":"CARTILAGE","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140628123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
CARTILAGEPub Date : 2024-04-16DOI: 10.1177/19476035241246609
Shaun Kai Kiat Chua, Walter-Soon-Yaw Wong, Don Thong Siang Koh, Rehena Sultana, Junwei Soong, Kong Hwee Lee, Hamid Rahmatullah Bin Abdul Razak
{"title":"Faster Bone Gap Union in Medial Opening Wedge High Tibial Osteotomy With 3D-Printed Synthetic Bioresorbable Polycaprolactone and Tricalcium Phosphate Osteotomy Gap Fillers Compared to Allogeneic Osteotomy Gap Fillers: A Retrospective Matched-Pair Cohort Study","authors":"Shaun Kai Kiat Chua, Walter-Soon-Yaw Wong, Don Thong Siang Koh, Rehena Sultana, Junwei Soong, Kong Hwee Lee, Hamid Rahmatullah Bin Abdul Razak","doi":"10.1177/19476035241246609","DOIUrl":"https://doi.org/10.1177/19476035241246609","url":null,"abstract":"ObjectiveThe use of synthetic bone substitute material (BSM) as osteotomy gap fillers have been reported to improve outcomes in medial opening wedge high tibial osteotomy (MOWHTO). This study aims to evaluate the early radiological outcomes (bone union) and complication rates of the novel patient-specific 3D-printed honeycomb-structured polycaprolactone and tricalcium phosphate (PCL-TCP) synthetic graft compared to allogeneic bone grafts as an osteotomy gap filler in MOWHTO.MethodsA retrospective matched-pair analysis of patients who underwent MOWHTO with either PCL-TCP synthetic graft or allogenic femoral head allograft as osteotomy gap filler was performed. The osteotomy gap was split into equal zones (Zone 1-5), and bone union was evaluated on anteroposterior radiographs based on the van Hemert classification at 1, 3, 6, and 12 months postoperatively. Postoperative complications including infection, lateral hinge fractures, and persistent pain was measured. The study and control group were matched for age, smoking status, diabetes mellitus, and osteotomy gap size.ResultsSignificantly greater bone union progression was observed in the PCL-TCP group than in the allograft group at 1 month (Zones 1-3), 3 months (Zones 1-4), 6 months (Zones 1-2, 4), and 12 months (Zones 2-3, 5) postoperatively ( P < 0.05). No significant difference in complications rates was noted between the two groups at 1 year.ConclusionsBone union rates observed in patients who underwent MOWHTO with the PCL-TCP synthetic graft osteotomy gap filler were superior to those in the allograft group at 1 year postoperatively, with no significant difference in complication rates (postoperative infection, lateral hinge fractures, and persistent pain).","PeriodicalId":9626,"journal":{"name":"CARTILAGE","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140614834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
CARTILAGEPub Date : 2024-04-15DOI: 10.1177/19476035241241930
John-Peter Bonello, M. Yat Tse, Trevor J. G. Robinson, Davide D. Bardana, Stephen D. Waldman, Stephen C. Pang
{"title":"Expression of Chondrogenic Potential Markers in Cultured Chondrocytes from the Human Knee Joint","authors":"John-Peter Bonello, M. Yat Tse, Trevor J. G. Robinson, Davide D. Bardana, Stephen D. Waldman, Stephen C. Pang","doi":"10.1177/19476035241241930","DOIUrl":"https://doi.org/10.1177/19476035241241930","url":null,"abstract":"ObjectivesWhile substantial progress has been made in engineering cartilaginous constructs for animal models, further research is needed to translate these methodologies for human applications. Evidence suggests that cultured autologous chondrocytes undergo changes in phenotype and gene expression, thereby affecting their proliferation and differentiation capacity. This study was designed to evaluate the expression of chondrogenic markers in cultured human articular chondrocytes from passages 3 (P3) and 7 (P7), beyond the current clinical recommendation of P3.MethodsCultured autologous chondrocytes were passaged from P3 up to P7, and quantitative polymerase chain reaction (qPCR) was used to assess mRNA expression of chondrogenic markers, including collagen type I (COLI), collagen type II (COLII), aggrecan (AGG), bone morphogenetic protein 4 (BMP4), transcription factor SOX-9 (SOX9), proteoglycan 4 (PGR4), and transformation-related protein 53 (p53), between P3 and P7.ResultsExcept for AGG, no significant differences were found in the expression of markers between passages, suggesting the maintenance of chondrogenic potential in cultured chondrocytes. Differential expression identified between SOX9 and PGR4, as well as between COLI and SOX9, indicates that differences in chondrogenic markers are present between age groups and sexes, respectively.ConclusionsOverall, expression profiles of younger and male chondrocytes exhibit conversion of mature cartilage characteristics compared to their counterparts, with signs of dedifferentiation and loss of phenotype within-group passaging. These results may have implications in guiding the use of higher passaged chondrocytes for engineering constructs and provide a foundation for clinical recommendations surrounding the repair and treatment of articular cartilage pathology in both sexes.","PeriodicalId":9626,"journal":{"name":"CARTILAGE","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140602902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
CARTILAGEPub Date : 2024-04-13DOI: 10.1177/19476035241244491
Julia S. Retzky, Connor Fletcher, Morgan Rizy, Alissa Burge, Sabrina M. Strickland
{"title":"Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) Scores > 55 at 6 Months Postoperative Predict Ability to Achieve Patient Acceptable Symptomatic State at Minimum 1 Year Postoperative Following Autologous Chondrocyte Implantation for Grade IV Chondral Defects About the Patellofemoral Joint","authors":"Julia S. Retzky, Connor Fletcher, Morgan Rizy, Alissa Burge, Sabrina M. Strickland","doi":"10.1177/19476035241244491","DOIUrl":"https://doi.org/10.1177/19476035241244491","url":null,"abstract":"PurposeThe primary aim is to evaluate the relationship between MOCART scores and patient satisfaction, as evaluated by achievement of (1) the Patient Acceptable Symptomatic State (PASS) and (2) the minimal clinically important difference (MCID) for Knee Injury and Osteoarthritis Score Quality of Life (KOOS QoL), for patients undergoing autologous chondrocyte implantation (ACI) for focal Grade IV patellofemoral chondral defects. The secondary aim is to determine the threshold MOCART score which predicts the ability to meet the PASS and the MCID for KOOS QoL.MethodsPatients undergoing ACI for grade IV patellofemoral chondral defects by a single surgeon from 2017 to 2020 were identified by search of the EMR. To determine PASS status, patients were asked, “Do you consider your current level of symptoms to be acceptable?” KOOS QoL scores were also collected. Patients with 6-month postoperative knee MRI, PASS scores, and minimum 2-year follow-up data were included. Paired t tests and Wilcoxon Rank-Sum tests were used to evaluate the relationship between MOCART scores and (1) PASS achievement and (2) achievement of the MCID for KOOS QoL (12.8).ResultsThirty-four patients were included, with a median age of 35.1 years [IQR: 24.6, 37.1], and BMI of 24.0 kg/m<jats:sup>2</jats:sup> [IQR: 21.5, 28.1]. The median time to postoperative MRI was 6.7 months [IQR: 5.8, 7.9], and average follow-up time was 3.7 ± 1.2 years. Twenty-five patients (74%) achieved PASS, and 18 patients (out of 27 who had postop KOOS QoL Scores, 67%) achieved the MCID for KOOS QoL. Patients who achieved PASS had higher average MOCART scores (61.8 ± 16.0) than those who did not achieve PASS (45.0 ± 12.8, p=0.011), whereas patients who achieved the MCID for KOOS QoL did not have higher MOCART scores than those who did not achieve the MCID (61.9 ± 18.3 versus 53.3 ± 17.1, P = 0.25). There was no relationship between age, sex, lesion size, and lesion location and ability to achieve PASS or MCID for KOOS QoL (p>0.05). A threshold MOCART value of 55 was associated with the highest AUC on ROC analysis for likelihood of achieving PASS (0.778) and MCID for KOOS QoL (0.667).ConclusionHigher MOCART scores are associated with an increased likelihood of achieving PASS following patellofemoral ACI. Moreover, MOCART scores > 55 predict the ability to achieve PASS and the MCID for KOOS QoL following patellofemoral ACI.Level of Evidence:IV","PeriodicalId":9626,"journal":{"name":"CARTILAGE","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140573398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
CARTILAGEPub Date : 2024-03-30DOI: 10.1177/19476035241240341
Ben Efrima, Agustin Barbero, Camilla Maccario, Cristian Indino, Chiara Nocera, Assaf Albagli, Jari Dahmen, Federico Giuseppe Usuelli
{"title":"Significant Clinical Improvement After Arthroscopic Autologous Matrix-Induced Chondrogenesis for Osteochondral Lesions of the Talus: A 5-Year Follow-Up.","authors":"Ben Efrima, Agustin Barbero, Camilla Maccario, Cristian Indino, Chiara Nocera, Assaf Albagli, Jari Dahmen, Federico Giuseppe Usuelli","doi":"10.1177/19476035241240341","DOIUrl":"https://doi.org/10.1177/19476035241240341","url":null,"abstract":"<p><strong>Purpose: </strong>This study aims to evaluate the clinical outcomes of arthroscopic autologous matrix-induced chondrogenesis (A-AMIC) for osteochondral lesions of the talus (OLT) at 24 months and 60 months of follow-up. The secondary aim was to assess whether age, body mass index (BMI), and lesion surface affect outcomes.</p><p><strong>Design: </strong>Sixty-three patients (32 males, 31 females) with a median age of 37 years [interquartile range (IQR): 25-48] were included. Preoperative and postoperative (24 months and 60 months) clinical outcomes were evaluated using a Visual Analog Score (VAS) for pain during walking, the American Orthopaedic Foot and Ankle Society (AOFAS), Short-Form Survey (SF-12), the Halasi, and the University of California, Los Angeles (UCLA) scores. Patients were categorized according to age, BMI, and lesion surface (1-1.5 cm<sup>2</sup> and over 1.5 cm<sup>2</sup>). The effect of each category was evaluated.</p><p><strong>Results: </strong>There were significant improvements in the VAS, AOFAS, SF-12, and UCLA, comparing the preoperative scores to the 60-month follow-up scores (<i>P</i> < 0.001). There were no significant differences in the above-mentioned outcomes between the follow-up periods. Patients older than 33 years had lower SF-12, Halasi, and UCLA scores (<i>P</i> = 0.005, 0.004, and <0.001, respectively). Overweight patients had lower VAS, SF-12, Halasi, and UCLA scores (<i>P</i> = 0.006, 0.002, 0.024, and 0.007, respectively). Lesion size was uninfluential.</p><p><strong>Conclusion: </strong>A-AMIC yielded clinical improvements at a minimum follow-up of 60 months in patients with symptomatic OLTs, with clinical improvement peaking in the first 2 years, followed by a plateau period. Increased age and BMI were significantly associated with inferior outcomes.</p>","PeriodicalId":9626,"journal":{"name":"CARTILAGE","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140329695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
CARTILAGEPub Date : 2024-03-25DOI: 10.1177/19476035241240361
Junjun Yang, Xin Wang, Yingbo Zhang, Rui He, Zhenlan Fu, Rong Wang, Yanming Ma, Dejie Fu, Shuo Meng, Wang Cai, Yizhao Zhou, Cheng Chen, Guangxing Chen, Xiaoyuan Gong
{"title":"Intra-Articular Injection of Interleukin-8 Neutralizing Monoclonal Antibody Effectively Attenuates Osteoarthritis Progression in Rabbits.","authors":"Junjun Yang, Xin Wang, Yingbo Zhang, Rui He, Zhenlan Fu, Rong Wang, Yanming Ma, Dejie Fu, Shuo Meng, Wang Cai, Yizhao Zhou, Cheng Chen, Guangxing Chen, Xiaoyuan Gong","doi":"10.1177/19476035241240361","DOIUrl":"https://doi.org/10.1177/19476035241240361","url":null,"abstract":"<p><strong>Objective: </strong>Cytokines are implicated in the pathogenesis of osteoarthritis (OA), and this study aims to assess the therapeutic potential of an IL-8 neutralizing monoclonal antibody (mAb) for OA intervention.</p><p><strong>Design: </strong>The study employed a rabbit model of OA induced by anterior cruciate ligament transection (ACLT) surgery to investigate the effects of an interleukin (IL)-8 neutralizing mAb, with hyaluronic acid (HA) used as a positive control. Primary outcomes assessed in the rabbits included cartilage repair, synovitis, joint effusion, changes in footprints, and lower limb loading conditions.</p><p><strong>Results: </strong>Compared to HA, intra-articular injection of the IL-8 neutralizing mAb demonstrated a more pronounced attenuation of OA progression and enhancement of cartilage repair. We observed a reduction in synovitis and joint effusion, indications of bone marrow edema, as well as improvements in lower limb function. In knees treated with the neutralizing IL-8 mAb, there was a significant decrease in IL-8 levels within the synovial tissues.</p><p><strong>Conclusions: </strong>The IL-8 neutralizing mAb exhibits promising therapeutic potential in the management of OA by attenuating inflammation and facilitating cartilage repair. However, further investigations are warranted to comprehensively elucidate the underlying mechanisms, optimize treatment protocols, and ensure the long-term safety and efficacy of this innovative therapeutic approach.</p>","PeriodicalId":9626,"journal":{"name":"CARTILAGE","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140206302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Evidence-Based Update on the Surgical Technique and Clinical Outcomes of Retrograde Drilling: A Systematic Review.","authors":"Youichi Yasui, Wataru Miyamoto, Yoshiharu Shimozono, Keisuke Tsukada, Hirotaka Kawano, Masato Takao","doi":"10.1177/19476035241239303","DOIUrl":"https://doi.org/10.1177/19476035241239303","url":null,"abstract":"<p><strong>Background: </strong>Retrograde drilling is an established surgical technique to treat osteochondral lesions of the talus (OLT). It involves non-trans-articular drilling to induce subchondral bone revascularization and bone formation without damaging the overlying articular cartilage. The present study aimed to elucidate the heterogeneity of clinical studies on retrograde drilling for OLT.</p><p><strong>Design: </strong>A systematic search of the MEDLINE, Web of Science, EMBASE, and Cochrane Library databases for studies published between January 1996 and August 27, 2022, was performed based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines by two independent reviewers. The included studies were evaluated for their level of evidence (LoE) and quality of evidence (QoE) using the Modified Coleman Methodology Score. Variables reporting surgical and clinical outcomes and complications were evaluated.</p><p><strong>Results: </strong>Eleven studies with 207 ankles were included (mean follow-up period = 31.1 months). The mean LoE was 3.8 (LoE 3: two studies, LoE 4: nine studies), and the mean QoE was 50.8 (fair: three studies, poor: eight studies). Ten studies used the American Orthopedic Foot and Ankle Society (AOFAS) score, which improved from 57.9 preoperatively to 86.1 postoperatively. The period and protocol of conservative treatment, lesion character, surgical technique, and postoperative protocol were inconsistent or underreported.</p><p><strong>Conclusions: </strong>This systematic review revealed that low LoE and poor QoE, coupled with heterogeneity among the included studies, impede definitive conclusions regarding the effectiveness of this technique. Consequently, well-designed clinical trials are essential to develop standardized clinical guidelines for using retrograde drilling in OLT.</p>","PeriodicalId":9626,"journal":{"name":"CARTILAGE","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140173830","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
CARTILAGEPub Date : 2024-03-19DOI: 10.1177/19476035241233659
Ellen G J Ripmeester, Jessica S J J Steijns, Karolina A P Wijnands, Roderick H M J Stassen, Vasek Pitelka, Laura C W Peeters, Andy Cremers, Nzekui M S A Astryde, Alzbeta Chabronova, Don A M Surtel, Pieter J Emans, Guus G H van den Akker, Bert van Rietbergen, Lodewijk W van Rhijn, Marjolein M J Caron, Tim J M Welting
{"title":"The BMP7-Derived Peptide p[63-82] Reduces Cartilage Degeneration in the Rat ACLT-pMMx Model for Posttraumatic Osteoarthritis.","authors":"Ellen G J Ripmeester, Jessica S J J Steijns, Karolina A P Wijnands, Roderick H M J Stassen, Vasek Pitelka, Laura C W Peeters, Andy Cremers, Nzekui M S A Astryde, Alzbeta Chabronova, Don A M Surtel, Pieter J Emans, Guus G H van den Akker, Bert van Rietbergen, Lodewijk W van Rhijn, Marjolein M J Caron, Tim J M Welting","doi":"10.1177/19476035241233659","DOIUrl":"https://doi.org/10.1177/19476035241233659","url":null,"abstract":"<p><strong>Objective: </strong>Osteoarthritis (OA) is characterized by articular cartilage erosion, pathological subchondral bone changes, and signs of synovial inflammation and pain. We previously identified p[63-82], a bone morphogenetic protein 7 (BMP7)-derived bioactive peptide that attenuates structural cartilage degeneration in the rat medial meniscal tear-model for posttraumatic OA. This study aimed to evaluate the cartilage erosion-attenuating activity of p[63-82] in a different preclinical model for OA (anterior cruciate ligament transection-partial medial meniscectomy [anterior cruciate ligament transection (ACLT)-pMMx]). The disease-modifying action of the p[63-82] was followed-up in this model for 5 and 10 weeks.</p><p><strong>Design: </strong>Skeletally mature male Lewis rats underwent ACLT-pMMx surgery. Rats received weekly intra-articular injections with either saline or 500 ng p[63-82]. Five and 10 weeks postsurgery, rats were sacrificed, and subchondral bone characteristics were determined using microcomputed tomography (µCT). Histopathological evaluation of cartilage degradation and Osteoarthritis Research Society International (OARSI)-scoring was performed following Safranin-O/Fast Green staining. Pain-related behavior was measured by incapacitance testing and footprint analysis.</p><p><strong>Results: </strong>Histopathological evaluation at 5 and 10 weeks postsurgery showed reduced cartilage degeneration and a significantly reduced OARSI score, whereas no significant changes in subchondral bone characteristics were found in the p[63-82]-treated rats compared to the saline-treated rats. ACLT-pMMx-induced imbalance of static weightbearing capacity in the p[63-82] group was significantly improved compared to the saline-treated rats at weeks 5 postsurgery. Footprint analysis scores in the p[63-82]-treated rats demonstrated improvement at week 10 postsurgery.</p><p><strong>Conclusions: </strong>Weekly intra-articular injections of p[63-82] in the rat ACLT-pMMx posttraumatic OA model resulted in reduced degenerative cartilage changes and induced functional improvement in static weightbearing capacity during follow-up.</p>","PeriodicalId":9626,"journal":{"name":"CARTILAGE","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140157587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
CARTILAGEPub Date : 2024-03-19DOI: 10.1177/19476035241235928
Christoph Gaissmaier, Peter Angele, Robert C Spiro, Annette Köhler, Alexandra Kirner, Philipp Niemeyer
{"title":"Hydrogel-Based Matrix-Associated Autologous Chondrocyte Implantation Shows Greater Substantial Clinical Benefit at 24 Months Follow-Up than Microfracture: A Propensity Score Matched-Pair Analysis.","authors":"Christoph Gaissmaier, Peter Angele, Robert C Spiro, Annette Köhler, Alexandra Kirner, Philipp Niemeyer","doi":"10.1177/19476035241235928","DOIUrl":"https://doi.org/10.1177/19476035241235928","url":null,"abstract":"<p><strong>Objective: </strong>To compare substantial clinical benefit (SCB) of a hydrogel-based, matrix-associated autologous chondrocyte implantation (M-ACI) method versus microfracture (MFx) in the treatment of knee cartilage defects.</p><p><strong>Design: </strong>Propensity score matched-pair analysis, using the MFx control group of a phase III study as comparator for M-ACI treatment in a single-arm phase III study, resulting in 144 patients in the matched-pair set.</p><p><strong>Results: </strong>Groups were comparable regarding baseline Knee Injury and Osteoarthritis Outcome Score (KOOS), sex, age, body mass index, symptom duration, smoking status, and previous knee surgeries. Defect sizes in the M-ACI group were significantly larger than in the MFx group (6.4 cm<sup>2</sup> vs. 3.7 cm<sup>2</sup>). Other differences concerned location, number, and etiology of defects that were not considered to influence the interpretation of results. At 24 months, significantly more patients in the M-ACI group achieved SCB in KOOS pain (72.2% vs. 48.6%; <i>P</i> = 0.0108), symptoms (84.7% vs. 61.1%, <i>P</i> = 0.0039), sports/recreation (84.7% vs. 56.9%, <i>P</i> = 0.0008), and quality of life (QoL; 72.2% vs. 44.4%, <i>P</i> = 0.0014). The SCBs for KOOS activities in daily living and International Knee Documentation Committee score were higher for M-ACI but not significantly different from MFx. The SCB rates consistently favored M-ACI from 3 months onward. The highest improvements from baseline at 24 months in patients with SCB were observed for KOOS sports/rec. (M-ACI: 60.8 points, MFx: 55.9 points) and QoL (M-ACI: 58.1, MFx: 57.4).</p><p><strong>Conclusion: </strong>Hydrogel-based M-ACI demonstrated superior SCB in KOOS pain, symptoms, sports/rec., and QoL compared with MFx in patients with knee cartilage defects through 2 years follow-up.</p>","PeriodicalId":9626,"journal":{"name":"CARTILAGE","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140157586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}