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Cartilage[JOURNAL]

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Mechanistic Insights into Cartilage Protection and Extracellular Matrix Remodeling: Transcriptome Analysis of Diclofenac Etalhyaluronate-Treated Knee Cartilage in Collagen-Induced Arthritis Rats and Cytokine-Stimulated Human Chondrocytes.

Kitani A, Takada S, Nozaki S … +7 more , Kojima K, Toyama K, Hashimoto T, Takeuchi J, Kawamoto A, Fujita T, Yoshioka K

Cartilage · 2025 Dec · PMID 41351286 · Full text

BackgroundDiclofenac etalhyaluronate (DF-HA, SI-613/ONO-5704) is a conjugate of hyaluronic acid (HA) and diclofenac (DF), and its intra-articular injection is widely used for the treatment of osteoarthritis in Japan. Whi... BackgroundDiclofenac etalhyaluronate (DF-HA, SI-613/ONO-5704) is a conjugate of hyaluronic acid (HA) and diclofenac (DF), and its intra-articular injection is widely used for the treatment of osteoarthritis in Japan. While novel mechanisms of cartilage protection by DF-HA have been identified, a comprehensive analysis of the biological responses unique to DF-HA has not yet been conducted.DesignWe used an RNA sequencing (RNA-seq) method to comprehensively analyze gene expression in the knee joint cartilage of arthritic rats and cytokine-stimulated chondrocytes. For the mechanistic analysis of DF-HA, genes that were downregulated or upregulated by DF-HA, HA, or DF were extracted. Pathway analysis was then performed on genes that specifically varied with DF-HA treatment.ResultsIn the cartilage of rats with collagen-induced arthritis, treatment with DF-HA, but not DF or HA, suppressed the extracellular matrix (ECM) remodeling pathway and promoted the parathyroid hormone/parathyroid hormone-related peptide receptor-mediated pathway, which regulates chondrocyte differentiation and bone/cartilage development. In cytokine-stimulated chondrocytes, DF-HA similarly suppressed the ECM remodeling pathway; specifically, gene expression changes in , and were consistent with those observed .ConclusionRNA-seq analysis of cartilage in arthritic rats and cytokine-stimulated chondrocytes provided molecular mechanistic insights, indicating that DF-HA treatment induced cartilage protection through the suppression of ECM remodeling.

Cell Co-Implantations With Chondrocytes for Cartilage Repair: A Systematic Review of Results.

Olijve WT, Penn TW, de Jong WC … +3 more , Korpershoek JV, de Girolamo L, Brittberg M

Cartilage · 2025 Dec · PMID 41342882 · Full text

ObjectivesDamaged articular cartilage cannot regenerate spontaneously. Chondrocyte therapy, the current treatment of choice, requires laboratory expansion, necessitating two surgical procedures. Adding a second cell type... ObjectivesDamaged articular cartilage cannot regenerate spontaneously. Chondrocyte therapy, the current treatment of choice, requires laboratory expansion, necessitating two surgical procedures. Adding a second cell type to intraoperatively isolated chondrocytes enables single-stage chondrocyte-based repair strategies and has shown promise . The benefit of this strategy and in the clinic has not yet been comprehensively assessed. This systematic review assesses the efficacy of cartilage repair by co-implantations of chondrocytes with other cell types over all available studies.DesignMedline, Embase and Cochrane databases were searched for studies on co-implantations of chondrocytes with other cell types for hyaline cartilage repair. For each study, extracted data were tabulated and reporting quality and risk of bias were assessed. Studies were categorized based on their control groups for qualitative synthesis.ResultsThe search yielded 48 studies across 46 publications: 44 animal studies (26 ectopic and 18 orthotopic) and four clinical trials. Ectopic studies scored poorly on reporting quality and bias, while orthotopic studies were only moderately better. Twenty-seven of 27 experiments with chondrocyte-only controls demonstrated synergistic cartilage formation through co-implantation. Cartilage formation by co-implantations was also found in 15 of 17 experiments without such control and in four clinical trials.ConclusionCartilage repair by articular chondrocytes is improved by adding a second cell type, like mesenchymal stromal cells. This is likely caused by the second cell types' stimulatory support. Other second cell types and chondrocyte sources have shown promising results too. This is encouraging for further clinical exploration of single-stage co-implantation strategies.

MiRNA-140-5p Modulates Cartilage Mechanical Environment by Preserving Surface Stress Homeostasis.

Li B, Chen G, Han L … +2 more , Li H, Zou N

Cartilage · 2025 Dec · PMID 41342411 · Full text

IntroductionThis study explores the interplay between miRNA-140-5p expression and mechanical stress in cartilage within joint biomechanics.MethodsTibial plateau specimens, CT data, and mechanical parameters were obtained... IntroductionThis study explores the interplay between miRNA-140-5p expression and mechanical stress in cartilage within joint biomechanics.MethodsTibial plateau specimens, CT data, and mechanical parameters were obtained from healthy and OA donors. Twenty-four mice, including 12 miRNA-140-5p knockdown (MUT-group) and 12 wild-type (WT group), underwent anterior-cruciate-ligament-transection (ACLT) or sham-operation (SHAM). Finite element analysis, 3D simulation, CT scans, immunohistochemical staining, and fluorescence in situ hybridization were conducted. Primary chondrocytes with or without miRNA-140-5p agomir were loaded mechanically and analyzed by RT-qPCR, Western blot, and phalloidin staining.ResultsThe mechanical coupling unit comprised articular cartilage and subchondral bone, with cartilage apparent compressive modulus linked to the trabecular bone structure ( < 0.05). Healthy-joint samples and low-stress regions in animal samples exhibited high miRNA-140-5p expression ( < 0.05) and low RhoA expression. OA or high-stress regions showed the opposite trend ( < 0.05). MiRNA-140-5p knockdown increased joint loading in mice. , miRNA-140-5p overexpression reduced RhoA and cytoskeletal remodeling, maintaining chondrocyte mechano-responsiveness.ConclusionsOur study reveals a link between mechanical stress and miRNA-140-5p, implying its role in maintaining joint mechanical homeostasis. These findings enhance understanding of biomechanical-molecular interplay, though further studies are needed to assess therapeutic potential in osteoarthritis.

Autologous Chondrocyte Implantation Combined with High Tibial Osteotomy for Spontaneous Osteonecrosis of the Knee with a Relatively Large Cartilage Lesion in Elderly Patients.

Kumagai K, Akamatsu T, Nejima S … +4 more , Choe H, Ike H, Kobayashi N, Inaba Y

Cartilage · 2025 Nov · PMID 41263050 · Full text

ObjectiveThis study aimed to evaluate clinical outcomes and cartilage repair following autologous chondrocyte implantation (ACI) combined with high tibial osteotomy (HTO) in elderly patients with spontaneous osteonecrosi... ObjectiveThis study aimed to evaluate clinical outcomes and cartilage repair following autologous chondrocyte implantation (ACI) combined with high tibial osteotomy (HTO) in elderly patients with spontaneous osteonecrosis of the knee (SONK) presenting with large cartilage defects.DesignEleven knees of 11 patients with SONK (lesion size ≥4 cm) aged 60 years or older underwent ACI and concomitant opening-wedge HTO. Patients were followed for at least 1 year. Clinical outcomes were assessed using the Knee Injury and Osteoarthritis Outcome Score (KOOS). Cartilage repair was evaluated arthroscopically using the International Cartilage Repair Society (ICRS) grade and histologically using the ICRS II score at second-look arthroscopy.ResultsThe overall KOOS improved significantly from a preoperative value of 38.4 ± 8.5 to a 1-year postoperative value of 77.8 ± 10.9 ( < 0.01). Arthroscopy showed cartilage repair to normal or nearly normal in 91% of cases. The mean histological ICRS II score was 67.5 ± 16.2. No postoperative complications or need for additional surgical interventions was observed.ConclusionsACI combined with HTO provides good clinical and histological outcomes in elderly patients with SONK and large cartilage defects. This approach represents an effective joint-preserving treatment option, even in patients aged 60 years or older.

Erratum to: The Sagittal Tibial Tubercle-Trochlear Groove Distance as a Measurement of Sagittal Imbalance in Patients With Symptomatic Patellofemoral Chondral Lesions.

Bi AS, Yanke AB

Cartilage · 2025 Nov · PMID 41243812 · Full text

PurposeTo clarify and standardize sagittal tibial tubercle-trochlear groove (sTTTG) numerical values in the literature.ResultsSagittal tibial tubercle-trochlear groove distance has been recently popularized as a quantita... PurposeTo clarify and standardize sagittal tibial tubercle-trochlear groove (sTTTG) numerical values in the literature.ResultsSagittal tibial tubercle-trochlear groove distance has been recently popularized as a quantitative marker of patellofemoral contact forces and correlated to patellofemoral chondral lesion incidence, size, and osteoarthritis. There remains controversy over the precise definition of sTTTG.ConclusionThe current erratum clarifies that a relatively anterior tibial tubercle compared to the trochlear groove is quantified as a positive sTTTG, whereas a relatively posterior tibial tubercle compared to the trochlear groove is quantified as a negative sTTTG.

Knee Bursae: A Comprehensive Review of Clinical Evaluation, Imaging Differentiation, and the Expanding Role of Biologic Therapies.

Hasan M, Berkovich Y, Khatib M … +6 more , Steinfeld Y, Sleiman A, Ben Zvi L, Abu Alhija A, Ginesin E, Yonai Y

Cartilage · 2025 Nov · PMID 41239892 · Full text

BackgroundKnee bursae are potential sources of anterior, medial, lateral, and posterior knee pain, yet many remain under-recognized in clinical practice. Emerging biological therapies offer promising, minimally invasive... BackgroundKnee bursae are potential sources of anterior, medial, lateral, and posterior knee pain, yet many remain under-recognized in clinical practice. Emerging biological therapies offer promising, minimally invasive options for resistant bursitis, but high-level evidence is limited for several bursal types.PurposeTo systematically review the anatomy, clinical presentation, imaging characteristics, treatment strategies, and outcomes of 11 distinct knee bursae, with emphasis on the role of biologic therapies.MethodsThis systematic review followed PRISMA guidelines. PubMed and Embase were searched (2000-2024) for studies addressing anatomy, diagnosis, imaging, treatment (conservative, injection-based, biologic, or surgical), and outcomes of knee bursae. Studies involving human subjects, published in English, and reporting clinical, imaging, or therapeutic data were included. Levels of Evidence (LOE) were assigned using Oxford criteria.ResultsA total of 76 studies were included. Several randomized controlled trials (LOE I) focused on pes anserine and OA-related bursitis, while additional Level II studies assessed PRP and corticosteroids. Data on rare bursae (e.g., LCL, deep infrapatellar) were primarily derived from imaging reviews and case series (LOE III-IV). Corticosteroid injections showed recurrence rates of 20% to 40%. PRP and PRP+HA demonstrated improved pain relief and reduced recurrence in selected bursae, although protocols remain heterogeneous.ConclusionConservative management remains first-line for most bursae. PRP-based therapies, especially in pes anserine and OA-related bursitis, offer promising alternatives in refractory cases. Although several Level I-II studies support their efficacy, additional high-quality RCTs are warranted-particularly for understudied bursae.

Leucine Attenuates Osteoarthritis via mTORC1/LXRα-Mediated Macrophage Reprogramming and Rspo2/β-Catenin Axis Suppression.

Zheng K, Zhang J, Liu W … +1 more , Xu B

Cartilage · 2025 Nov · PMID 41200799 · Full text

ObjectiveThis study investigates the molecular mechanism by which leucine (Leu) ameliorates collagenase-induced osteoarthritis (CIOA) through macrophage polarization regulation.MethodsA CIOA mouse model was established a... ObjectiveThis study investigates the molecular mechanism by which leucine (Leu) ameliorates collagenase-induced osteoarthritis (CIOA) through macrophage polarization regulation.MethodsA CIOA mouse model was established and evaluated by micro-computed tomography (micro-CT) and histopathological analysis. Leu intervention was administered, and its therapeutic effects on cartilage degeneration and osteophyte formation were assessed. Integrated multi-omics analyses and mechanistic assays were performed to explore the role of the mTORC1/LXRα pathway in synovial macrophage reprogramming and its regulation of the Rspo2/β-catenin axis in chondroprogenitors. Functional validation was conducted using the LXRα inhibitor GSK2033.ResultsLeu intervention demonstrated significant therapeutic effects, reducing cartilage degeneration by 42% (Osteoarthritis Research Society International [OARSI] score) and osteophyte formation by 58% (volume reduction). Integrated multi-omics and mechanistic assays indicated that Leu activated mTORC1/LXRα to reprogram synovial macrophages toward an M2-like state, suppressed Rspo2, and attenuated β-catenin signaling in chondroprogenitors, thereby improving cartilage function. Functional validation using LXRα inhibitor GSK2033 confirmed pathway specificity, reversing Leu-mediated cartilage protection and reactivating osteogenic differentiation.ConclusionThese findings establish a novel "metabolism-immunity-cartilage" axis in which Leu coordinates mTORC1/LXRα-driven macrophage reprogramming with Rspo2/β-catenin axis suppression, offering dual-target therapeutic potential for osteoarthritis. The study redefines nutritional amino acids as immunometabolic modulators in degenerative joint diseases, proposing Leu supplementation as a viable strategy for interrupting the inflammation-bone remodeling cycle in traumatic arthritis. No clinical trials were involved in this preclinical investigation.

Bone Marrow Aspirate Concentrate to Treat Ankle Osteoarthritis: A Narrative Review of Progress and Challenges.

Hines SE, Makarczyk MJ, Heidinger E … +3 more , Shang J, Lin H, Hogan MV

Cartilage · 2025 Nov · PMID 41174981 · Full text

ObjectiveCurrently, there is a wide range of therapeutics that can be used to treat ankle osteoarthritis (OA), but none of them are able to fully restore the function of the ankle joint long-term. In this narrative revie... ObjectiveCurrently, there is a wide range of therapeutics that can be used to treat ankle osteoarthritis (OA), but none of them are able to fully restore the function of the ankle joint long-term. In this narrative review, we aim to summarize the current progress of using bone marrow aspirate concentrate (BMAC) for treating ankle OA.DesignPubMed was searched for publications that were published from 1990 until September 1, 2025 (moment of search). Key search terms were bone marrow aspirate concentrate and ankle OA. This yielded 17 hits, of which 10 were included in this narrative review.ResultsBMAC may enhance cartilage repair in ankle injuries and OA, especially when it is used in combination with other surgical techniques and biological treatments. However, the body of supporting evidence remains largely composed of Level II to IV studies (case-control and retrospective series). In addition, the independent role of BMAC remains unclear due to the lack of studies evaluating BMAC as a stand-alone treatment, as well as the unclear role that it plays as an adjuvant therapy.ConclusionsIn conclusion, the existing literature investigating BMAC for ankle OA is encouraging but remains inconclusive. High-quality randomized controlled trials with standardized protocols, longer follow-up, and head-to-head comparison against other treatment options are needed to establish both efficacy and cost-effectiveness. Establishing minimal reporting standards for BMAC composition is also critical to improve consistency across studies.

A Comprehensive Review of Auto- and Allogeneic Chondrocyte Transplantation in Animals and Humans From 1965 to 2025.

Osiecka-Iwan A, Hyc A, Malejczyk J … +1 more , Moskalewski S

Cartilage · 2025 Oct · PMID 41126523 · Full text

ObjectiveTo review the history of chondrocyte transplantation, new approaches to treatment of human chondral and osteochondral defects, animal experiments, the choice of chondrocytes for transplantation, immunological fe... ObjectiveTo review the history of chondrocyte transplantation, new approaches to treatment of human chondral and osteochondral defects, animal experiments, the choice of chondrocytes for transplantation, immunological features of human and animal chondrocytes and factors which could influence results of chondrocyte transplantation.DesignAs the material for review served numerous papers collected during our many years' chondrocyte studies supplemented by PubMed search.ResultsAutologous chondrocytes, expanded in culture, were successfully used to repair damaged human articular cartilage. Numerous modifications of the original procedure benefited from a better understanding of factors influencing chondrocyte differentiation. Immunological studies suggested that survival of allogeneic transplants of bioengineered human neocartilage may depend on both passive and active mechanisms of immune evasion. Human chondrocytes with deleted expression of MHC class I molecules produced cartilage which, after transplantation into monkey articular cartilage was attacked by NK cells.ConclusionsImmune response against human chondrocytes requires further investigation. It is already established that allogeneic chondrocytes are safe for treating chondral defects but not for healing osteochondral defects. Full reconstruction of cartilage defects by restoring anatomically identical hyaline cartilage seems not feasible.

FKBP38 Alleviates Osteoarthritis Progression by Inhibiting Chondrocyte Senescence.

Wu J, Chen W, Zou Z … +8 more , Li H, Zhou T, Liao Z, Rao Z, Li K, Tan X, Cao H, Wang H

Cartilage · 2025 Oct · PMID 41046448 · Full text

ObjectiveOsteoarthritis (OA) is a prevalent age-related degenerative joint disease characterized by cartilage degeneration, joint pain, and reduced mobility, with aging as the primary risk factor. This study aimed to inv... ObjectiveOsteoarthritis (OA) is a prevalent age-related degenerative joint disease characterized by cartilage degeneration, joint pain, and reduced mobility, with aging as the primary risk factor. This study aimed to investigate the role and mechanism of FK506 binding protein 38 (FKBP38) in chondrocyte senescence and OA progression.MethodsFKBP38 expression was detected in articular cartilage from natural aging and OA mouse models. Mice with FKBP38 conditional knockout (FKBP38-cKO) and inducible conditional knockout (FKBP38-iKO) were generated for these models. An adeno-associated virus (AAV) vector overexpressing FKBP38 was injected into wild-type mouse joints. Joint damage was assessed at 8 and 18 months for natural aging or 4 and 8 weeks after DMM surgery by histology.ResultsFKBP38 expression was downregulated in cartilage from both natural aging and OA mice. FKBP38 overexpression protected against H2O2-induced senescence in chondrocytes. Addition of rapamycin to inhibit mTORC1 signaling rescued the enhanced senescence and catabolism caused by FKBP38 knockdown in chondrocytes. Conditional deletion of FKBP38 in chondrocytes significantly accelerated senescence and aggravated both natural aging and OA progression by activating mTORC1 signaling, whereas overexpression of FKBP38 delayed these processes.ConclusionThese results indicate that FKBP38 protects against chondrocyte senescence and cartilage degradation to alleviate OA progression by inhibiting mTORC1 signaling.

Non-Operative Management for Osteochondral Lesions of the Tibial Plafond Results in Minor Improvements of Patient-Reported Outcomes: A 2-Year Prospective Follow-Up Study.

Rikken QGH, Dahmen J, Stufkens SAS … +1 more , Kerkhoffs GMMJ

Cartilage · 2025 Sep · PMID 41014285 · Full text

ObjectiveOsteochondral lesions of the tibial plafond (OLTP) are considered rare, and to date the treatment for these lesions has solely focused on operative management. The aim of this study was to prospectively assess t... ObjectiveOsteochondral lesions of the tibial plafond (OLTP) are considered rare, and to date the treatment for these lesions has solely focused on operative management. The aim of this study was to prospectively assess the 2-year patient-reported outcomes, radiological outcomes, and adverse outcomes for the non-operative treatment of patients with a symptomatic OLTP.DesignEighteen patients with a symptomatic OLTP who underwent non-operative treatment were prospectively assessed. The primary outcome concerned the numeric rating scale (NRS) for pain during weightbearing from baseline to 2-year follow-up. Secondarily, the patient-reported outcomes (PROMs) NRS during rest, running, and stairclimbing, as well as the Foot and Ankle Outcome Score (FAOS) and short-form-36 (SF-36) questionnaires were assessed. CT scans at median 2 years (IQR: 1.5-2) follow-up were reviewed for changes in lesion volume or signs of lesion healing. Return to sports and work rates were evaluated. The conversion to surgery rate and any complications were assessed.ResultsThe NRS during weightbearing improved (non-significantly) from a median of 5 (IQR: 3-7) out of 10 at baseline to 2 (IQR: 1-6) out of 10 at 2-year follow-up, = 0.06. The other NRS subscales, FAOS subscales, and SF-36 did not significantly improve at final follow-up. The follow-up CT-evaluation showed that lesion volume did not change (219 [IQR: 79-890] mm) compared to baseline (226 [IQR: 79-890] mm), = 0.2. In 10 (77%) out of 13 cases, signs of lesion filling or no change was observed. At final follow-up, 93% (13/14) of patients returned to any level of sports, 54% (7/13) of patients returned to preinjury level of sports, and 94% (15/16) of patients returned to work. No adverse events were observed, and 1 (6%) case converted to surgery.ConclusionsNon-operative management for OLTP resulted in minor improvements of patient-reported pain and functional outcomes up to 2-year follow-up. The conversion to surgery rate was 6%. Radiologically, lesion size and filling were found to remain stable at CT follow-up. Moreover, on average 9 out of 10 patients were able to participate in sport and could return to, or remain at, their preinjury work activities.

The Effect of Different Saline Suspension Height on Injured Articular Cartilage During Arthroscopic Surgery.

Gao Z, Huang Y, Kong S … +6 more , Yan W, Yang S, Hu F, Cheng J, Hu X, Shi W

Cartilage · 2025 Sep · PMID 40995932 · Full text

ObjectiveSaline is typically suspended at a certain height to maintain a clear surgical field in arthroscopic surgery. The effects of saline on cartilage have been extensively studied; however, the impact of the pressure... ObjectiveSaline is typically suspended at a certain height to maintain a clear surgical field in arthroscopic surgery. The effects of saline on cartilage have been extensively studied; however, the impact of the pressure generated by saline solution suspended at different heights on injured cartilage is largely unknown. This study investigates suspension-height-dependent cellular responses and tissue damage in traumatized cartilage.MethodsOsteochondral explants were harvested from porcine stifle joints, then were cut perpendicularly before immersed or irrigated for 2 hours with saline at 4 heights (80/105/130/155 cm). The explants were then transferred to and cultured in chondrogenic medium for 5 days. Chondrocytes viability was subsequently assessed with confocal imaging. Cell response was assessed with expression levels of proapoptosis and proinflammatory genes. Tissue damage was evaluated by secretome analysis of proinflammatory cytokines and extracellular matrix and histological test.ResultsIrrigation exacerbated cut-induced chondrocytes death in superficial zone of cartilage, with mild change on 80 cm, 105 cm, 130 cm and severe damage on 155 cm. Similarly, explants that underwent irrigation with heights of 80 cm to 130 cm exhibited relatively slighter change of gene expression of BAX, BCL2, IL-6 and NOS2 and release of GAG, IL-6 and NO to a comparable extent.ConclusionThis study provides evidence of damaging effects of irrigation on injured cartilage surface. Suspension heights of 80 cm to 130 cm led to comparable minor cartilage damage.

Equine Bone Marrow-Derived MSCs and Their EVs Exhibit Different Immunomodulatory Effects on Cartilage Explants in an Osteoarthritis Model.

Gaesser AM, Cianci JM, Even K … +6 more , Linardi RL, Ruthel G, Barot D, Elkhenany H, Engiles JB, Ortved KF

Cartilage · 2025 Sep · PMID 40995888 · Full text

ObjectiveTo compare the effects of equine MSCs and their extracellular vesicles (EV) on stimulated cartilage explants and assess how serum type influences EV production and cartilage inflammation.MethodsEVs were isolated... ObjectiveTo compare the effects of equine MSCs and their extracellular vesicles (EV) on stimulated cartilage explants and assess how serum type influences EV production and cartilage inflammation.MethodsEVs were isolated from bone marrow-derived MSCs cultured in equine serum (ES) or fetal bovine serum (FBS) media and concentrated via ultracentrifugation. Cartilage explants were stimulated with IL-1β and TNF-α and treated with MSCs, EVs, or left untreated. Cartilage explants were analyzed for cytokine concentration and examined for gene expression, glycosaminoglycan depletion, and histology.ResultsEVs produced by MSCs cultured in ES or FBS had similar characteristics. Cartilage explants treated with MSCs in ES media had decreased concentrations of IL-1β and increased concentrations of IL-6 in the supernatant compared to cartilage explants alone. Treatment with EVs did not significantly alter supernatant mediators. Cartilage explants cultured in ES had higher levels of IL-1β, IL-6, and TNF-α, while cartilage explants cultured in FBS had higher levels of PGE2. Treatment of stimulated cartilage explants with either MSCs or EVs did not alter gene expression or support extracellular matrix (ECM) degradation.ConclusionEquine MSCs appear to have enhanced immunomodulatory properties compared to EVs when used to treat stimulated cartilage explants. While some beneficial alterations in culture supernatants were detected, ECM degradation was not affected by treatment.

Interleukin-37 Ameliorates Articular Cartilage Damage in Two Murine Models of Osteoarthritis.

van Geffen EW, van Beuningen HM, Aarts J … +8 more , Vitters EL, Rijnen WHC, Blom AB, van de Loo FAJ, Blaney Davidson EN, Koenders MI, van Caam APM, van der Kraan PM

Cartilage · 2025 Sep · PMID 40970517 · Full text

ObjectiveIn this study, we investigated whether interleukin (IL)-37 ameliorates experimental osteoarthritis (OA).MethodsThe effects of IL-37 were investigated in collagenase-induced OA (CiOA) and destabilization of the m... ObjectiveIn this study, we investigated whether interleukin (IL)-37 ameliorates experimental osteoarthritis (OA).MethodsThe effects of IL-37 were investigated in collagenase-induced OA (CiOA) and destabilization of the medial meniscus (DMM). Human IL-37-adenovirus (ad-IL-37) was injected into the affected knee joint 4 and 18 days after the induction of OA. Luciferase-adenovirus was injected as control. Mice were sacrificed for histology at early and late stage of OA development. Interleukin-37 protein expression was confirmed by immunohistochemistry. Cartilage damage, osteophyte size and joint capsule thickness were measured. The effectiveness of ad-IL-37 was confirmed in vitro in human OA fibroblasts using real-time qualitative polymerase chain reaction (RT-qPCR) and Western blotting.ResultsInterleukin-37 protein expression was visible for at least 7 days after injection. At day 28, 10 days after the second injection, no clear synovial IL-37 staining was found any more, in both models. At day 28 of CiOA, ad-IL-37 significantly reduced articular cartilage damage and this was still reduced, although not significantly, at the late time point (day 42). In the DMM model, significant beneficial effect of IL-37 on cartilage damage was found at the late time point. In both OA models ad-IL-37 injections reduced the size of osteophytes.ConclusionInterleukin-37 ameliorated OA-induced articular cartilage damage and osteophyte formation in both models.

Cartilage Redox Balance Is Influenced by Substrate Availability.

Wang J, Henak CR

Cartilage · 2025 Sep · PMID 40970505 · Full text

PurposeThe mechanobiological response of cartilage redox balance might change in response to altered substrate availability. The purpose of this study is to investigate effects of key metabolic substrates (glucose, gluta... PurposeThe mechanobiological response of cartilage redox balance might change in response to altered substrate availability. The purpose of this study is to investigate effects of key metabolic substrates (glucose, glutamine, and oxygen) on the mechanoresponsiveness of cartilage redox balance using a label-free imaging technique that measures autofluorescence from endogenous redox cofactors.FindingsCompared with room oxygen tension, low oxygen tension had higher autofluorescence intensity in green (FAD) channel after a single sub-failure tensile load. Cartilage explants cultured in high glucose medium with glutamine supply had higher autofluorescence intensity in both channels (FAD and NADH/NADPH) compared with low glucose with glutamine group or high glucose without glutamine group, while no difference was observed between the latter 2 groups.ConclusionsLow oxygen tension or high glucose culture medium with glutamine supply increases the mechanoresponsiveness of cartilage redox balance induced by sub-failure mechanical loading. Glutamine appears to partially serve as a glucose substitute in this process.

Arthroscopic Debridement Combined With Platelet-Rich Plasma is a Viable Option for the Treatment of Advanced Ankle Osteoarthritis.

Miura T, Jujo Y, Tan JH … +2 more , Man CK, Takao M

Cartilage · 2025 Sep · PMID 40970333 · Full text

ObjectiveTo assess the efficacy of arthroscopic debridement combined with platelet-rich plasma (PRP) therapy in treating advanced ankle osteoarthritis (OA).DesignThe data of 34 advanced ankle OA patients were retrospecti... ObjectiveTo assess the efficacy of arthroscopic debridement combined with platelet-rich plasma (PRP) therapy in treating advanced ankle osteoarthritis (OA).DesignThe data of 34 advanced ankle OA patients were retrospectively analyzed, with 17 patients undergoing arthroscopic debridement alone (No-PRP group) and 17 receiving debridement with PRP therapy (PRP group). The Self-Administered Foot Evaluation Questionnaire (SAFE-Q) was evaluated preoperatively and at 3, 6, and 12 months postoperatively. The complications were assessed throughout the follow-up period.ResultsIn the PRP group, all SAFE-Q subscales significantly improved at 6- and 12-month post-treatment compared with baseline ( < 0.05), whereas improvements in the No-PRP group were limited. For severe ankle OA patients, only the pain-related subscale of the SAFE-Q significantly improved from baseline in the No-PRP group ( < 0.05). In contrast, all SAFE-Q subscales demonstrated significant improvement at 12 months postoperatively in the PRP group ( < 0.05). The recurrence rates were 23.5% in the No-PRP group and 11.8% in the PRP group.ConclusionArthroscopic debridement combined with PRP therapy for advanced ankle OA significantly improved all SAFE-Q subscales postoperatively, whereas debridement alone had limited benefits. This combination may offer an effective treatment for advanced ankle OA.

Anterior Closed Wedge High Tibial Osteotomy for Slope Correction in Anterior Cruciate Ligament Insufficiency: A Preliminary Report of 100 Cases at a 2-Year Follow-up.

Dickschas J, Schubert I, Wagner M … +3 more , Biedermann L, Simon M, Weiler A

Cartilage · 2025 Sep · PMID 40955063 · Full text

Clinical RelevanceIn recent years, an increased posterior tibial slope has been identified as a nonmodifiable risk factor for anterior cruciate ligament (ACL) injury and increased failure rates after ACL reconstruction (... Clinical RelevanceIn recent years, an increased posterior tibial slope has been identified as a nonmodifiable risk factor for anterior cruciate ligament (ACL) injury and increased failure rates after ACL reconstruction (ACLR). To date, the literature consists of clinical case series on slope reducing high tibial osteotomies and reports promising clinical results. However, higher case numbers are still lacking. The goal of the present series of anterior-closed-wedge high tibial osteotomies (ACW-HTO) was to analyze patient-reported outcome measures (PROMs) at a minimum of 2 years. It was hypothesized that an ACW-HTO with secondary ACLR after failed ACL surgery improves clinical outcome as compared with the pre-osteotomy state or can even give sufficient stability to avoid the need for revision ACLR.Material and methodsOne hundred consecutive cases with an ACW-HTO operated between February 2019 and December 2022 were included in 2 surgical centers (57 cases radiographic/51 cases with PROMs Sozialstiftung Bamberg and 43 cases radiographic/35 cases with PROMs Sporthopaedicum Berlin, Germany). The pre-injury (before first injury), the preoperative (before ACW-HTO), and the final postoperative conditions were documented using PROMs.ResultsThe mean follow-up was 36 months (SD ±11, range 24-82), the follow-up rate for the PROMs was 85%. The mean preoperative slope of 14.6° (SD ±2.4°; range 11°-28°), measured according to the method of Dejour and Bonnin, was corrected to a mean of 6.8° (SD ±2.0°; range 0°-12°), < 0.0001. No relevant complications were noted and no recurrent ACL graft failure was reported within the full follow-up period. Twenty-one patients had not received a revision ACLR after ACW-HTO at final follow-up due to sufficient stability. Prior to the first ACL injury, the mean Tegner activity scale was 7.3 points (SD ±1.7; 3-10) and mean Lysholm score revealed 98 points (SD ±4; range 79-100). Prior to ACW-HTO Tegner Scale was significantly reduced to 3.3 points (SD ±1.8; range 0-9) ( < 0.0001) and Lysholm score revealed 57 points (SD ±28; range 14-94) ( < 0.0001) as compared with the pre-injury level. At final follow-up, mean Tegner activity scale changed to 4.8 points (SD ±1.9; range 0-9), which significantly improved as compared with the pre-osteotomy stage ( < 0.0001). Of 85 patients, 18 achieved their pre-injury Tegner activity level, 2 even reached a level higher than the preoperative level. So the return to pre-injury activity level is 21%. The Lysholm score significantly improved to 83 points. (SD ±18; range 24-100) ( < 0.0001) as compared with the pre-osteotomy stage.ConclusionThe present case series presents the largest published series after ACW-HTO and secondary ACLR. Clinical and radiographic results underline that this procedure is safe and significantly increases the patient's ability to participate in light sports and activities of daily living due to an improved stability. An important fact is that 21% of patients after ACW-HTO have not needed a revision ACLR due to an improvement of stability after the osteotomy.

Socioeconomic Area Deprivation is Related to Poorer Patient-Reported Outcomes Following Autologous Chondrocyte Implantation (ACI).

Ismael ST, McCarthy HS, Wright K … +6 more , Williams M, Barnett A, Gallacher P, Jermin P, Roberts S, Kuiper JH

Cartilage · 2025 Sep · PMID 40905642 · Full text

ObjectiveTo determine the association between socioeconomic deprivation and short-term patient-reported clinical outcomes following autologous chondrocyte implantation (ACI).DesignAll patients receiving knee ACI between... ObjectiveTo determine the association between socioeconomic deprivation and short-term patient-reported clinical outcomes following autologous chondrocyte implantation (ACI).DesignAll patients receiving knee ACI between 1996 and 2020 in our center were identified. Socioeconomic deprivation of their residential area was quantified using the Index of Multiple Deprivation (IMD). Patient-reported 1-year Lysholm and Intermittent and Constant Osteoarthritis Pain (ICOAP) scores were used as outcome measures in the analyses. After transformation to ensure normal distributions (where required), linear multivariable regression was used to analyze the relationship between IMD and 1-year Lysholm score, adjusting for demographic characteristics (age, sex, body mass index [BMI], and smoking) and baseline Lysholm.ResultsThree hundred and ninety-one patients with a mean age of 50 years (range = 16-84; 266 male) were identified. Median BMI was 27 (17-47), with 138 patients overweight and 105 obese. Seventy-seven patients lived in upper and 41 in lower quintile deprivation areas. The mean baseline Lysholm score was 49.8 ± 17.3 SD, improving to 66.5 ± 21.3 SD at 1 year. Mean 1-year Lysholm scores were significantly lower with increasing area deprivation scores, adjusted for demographic factors. Specifically, areas with high unemployment levels, being female, or having a lower baseline Lysholm were associated with poorer outcomes, but age, BMI, smoking, or higher income deprivation were not.ConclusionThis study demonstrates poorer functional outcomes following ACI in patients from more deprived areas, indicating future studies should consider neighborhood deprivation as a confounding factor. Furthermore, targeting patients from areas with higher deprivation with additional interventions/community support may improve their outcomes.

Enhanced Superficial Zone Chondrocyte Expansion and Redifferentiation by Culture on Chondrocyte-Derived Decellularized Matrices.

Manzoni TJ, Ho A, Smull L … +6 more , West VC, Waters JDV, Lemus K, Adams J, Su AW, Parreno J

Cartilage · 2025 Aug · PMID 40886119 · Full text

BackgroundCell-based therapies to regenerate native-like cartilage are limited by the inability to re-express zone-specific molecules. While monolayer-expanded (passaged) chondrocytes are a clinically approved cell sourc... BackgroundCell-based therapies to regenerate native-like cartilage are limited by the inability to re-express zone-specific molecules. While monolayer-expanded (passaged) chondrocytes are a clinically approved cell source, the resulting tissues have reduced Proteoglycan-4 (PRG4) expression. This may be due to poor attachment, slow proliferation, and dedifferentiation of superficial zone chondrocytes (SZC) on polystyrene. Optimizing expansion conditions is therefore critical. Chondrocyte-derived decellularized extracellular matrix (CD-ECM) has been shown to enhance proliferation and reduce dedifferentiation of full-thickness chondrocytes, but its effect on SZC remains unknown. We tested the hypothesis that culturing SZC on CD-ECM would improve attachment, proliferation, and reduced dedifferentiation, enabling formation of PRG4-expressing tissue.MethodsPrimary bovine SZC were seeded on polystyrene or CD-ECM. Attachment, expansion rate, and gene expression were evaluated during passaging. Cells from each condition were assessed for their capacity to form PRG4-expressing bioengineered tissue.ResultsPrimary bovine SZC had increased attachment and reached confluency faster on CD-ECM. SZC on CD-ECM were smaller, with fewer actin stress fibers, and exhibited reduced expression of dedifferentiation markers. Furthermore, SZC expanded on CD-ECM were stimulated to form tissues rich in Collagen II and Aggrecan with higher Proteoglycan-4 expression.ConclusionsThe use of CD-ECM for passaging SZC may aid in achieving an adequate number of SZC for bioengineering purposes.

Plasma Amino Acids Reflect Cartilage Loss, Osteoarthritis Pain, Functional Disability, and Mental Health in a Longitudinal Study with Total Knee Replacement.

Mustonen AM, Säisänen L, Karttunen L … +7 more , Julkunen P, Esrafilian A, Reijonen J, Mäki J, Kröger H, Arokoski J, Nieminen P

Cartilage · 2025 Aug · PMID 40785121 · Full text

ObjectiveBiofluid amino acids (AAs) are potential biomarkers and therapeutic targets for knee osteoarthritis (KOA), a disease continuum of both mechanical and inflammatory aspects. Our aim was to identify AAs that would... ObjectiveBiofluid amino acids (AAs) are potential biomarkers and therapeutic targets for knee osteoarthritis (KOA), a disease continuum of both mechanical and inflammatory aspects. Our aim was to identify AAs that would associate with cartilage degradation, subjectively and objectively assessed joint pain and function, and psychological well-being.DesignFasting blood was sampled from 8 healthy controls at baseline, and from 8 end-stage KOA patients before total knee arthroplasty and 1 year post-operatively. Plasma AA profiles were determined with high-performance liquid chromatography, and the obtained results were analyzed with univariate and multivariate statistical tests, and with pathway analysis by MetaboAnalyst.ResultsCystine, -alanine, and hydroxylysine emerged as potential biomarkers distinguishing KOA patients from controls, and several metabolic pathways were disturbed in baseline KOA. Total knee arthroplasty reduced pain and improved joint function, but the effects on plasma AA metabolism were less obvious. There were significant associations between systemic AA levels and articular cartilage thickness, KOA pain, physical performance, corticospinal excitability, and mental health, independent of age and body adiposity.ConclusionThe results suggest that AA metabolism could play a role in KOA pathophysiology and motivate further studies investigating the potential of AAs as diagnostic biomarkers and therapeutic targets.
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