Cartilage[JOURNAL]
Sun
200 papers
Effects of Etanercept on Experimental Osteoarthritis in Rats: Role of Histone Deacetylases.
Wen ZH, Tang CC, Lin YY … +5 more , Yao ZK, Hsieh SP, Gar-Hwa-Lai, Chen WF, Jean YH
Cartilage · 2026 Jun · PMID 39057748 · Full text
ObjectiveMounting 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 ef...
ObjectiveMounting 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.MethodsInduction 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.ResultsACLT + 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.ConclusionOur 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.
Acellular Aragonite-Based Scaffold for the Treatment of Joint Surface Lesions of the Knee: A Minimum 5-Year Follow-Up Study.
de Caro F, Vuylsteke K, Van Genechten W … +1 more , Verdonk P
Cartilage · 2024 Dec · PMID 38899593 · Full text
OBJECTIVE: A novel aragonite-based scaffold has been developed. In this study, mid-term clinical and magnetic resonance imaging (MRI) results on 12 patients affected by isolated chondral or osteochondral lesions of the k...
OBJECTIVE: A novel aragonite-based scaffold has been developed. In this study, mid-term clinical and magnetic resonance imaging (MRI) results on 12 patients affected by isolated chondral or osteochondral lesions of the knee treated by the scaffold implantation have been evaluated at a mean follow-up of 6.5 (range: 5-8) years. DESIGN: The study population consisted of 3 females and 9 males, mean age 34.4 (20-51) years. The lesion was located on the medial femoral condyle, the trochlea, and the lateral femoral condyle in 5, 5, and 2 patients, respectively. In all cases, a single lesion over grade 3 of the International Cartilage Restoration and Joint Preservation Society (ICRS) classification was treated: in 9 cases by implantation of one plug, and in 2 cases with 2 plugs; the mean size of the lesion was 2.5 cm (1-7). RESULTS: One patient failed and was revised with a custom-made metal implant (Episealer). Overall, Knee Injury and Osteoarthritis Outcome Score (KOOS) significantly improved from 45 ± 13 preoperatively to 86 ± 13 at final follow-up. All KOOS subscales improved significantly: pain subscale increased from 48 ± 12 to 92 ± 11; symptoms from 66 ± 13 to 91 ± 13; activity of daily living (ADL) from 60 ± 19 to 90 ± 21; sport from 23 ± 20 to 75 ± 20; finally, quality of life (QoL) increased from 27 ± 14 to 77 ± 19. Long-term MRI MOCART score was 64. CONCLUSIONS: This study shows continued significant clinical improvement and good magnetic resonance imaging (MRI) findings with a minimum 5 years follow-up after implantation of a novel aragonite derived scaffold for the treatment of cartilage lesions of the knee. One patient failed and was revised with a custom-made metal implant (Episealer).
Investigating the Potential of Multilineage Differentiating Stress-Enduring Cells for Osteochondral Healing.
Watanabe S, Hosokawa H, Sakamoto T … +6 more , Horii M, Ono Y, Kimura S, Yamaguchi S, Ohtori S, Sasho T
Cartilage · 2026 Jun · PMID 38887038 · Full text
ObjectiveMultilineage 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 multipo...
ObjectiveMultilineage 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 , the dynamics , and the reparative contribution of Muse cells to osteochondral lesions.DesignLabeled 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 . Twenty-one immunocompromised mice were used as the models of osteochondral lesions. Live imaging, macroscopic evaluation, and histological and immunohistochemical analyses were conducted at the 4- and 8-week time points.ResultsMuse 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.ConclusionThe 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 than non-Muse cells.
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.
Bjerre-Bastos JJ, Sejersen C, Nielsen HB … +11 more , Boesen M, Secher NH, Distajo G, Flood V, Henrotin Y, Uebelhoer M, Krustrup P, Kitchen CC, Thudium CS, Andersen JR, Bihlet AR
Cartilage · 2025 Jun · PMID 38853398 · Full text
ObjectiveTo investigate how running, cycling, and sedentary cardiovascular stress impact biomarkers of cartilage turnover acutely in subjects with knee osteoarthritis (OA).DesignThis was a sequential, cross-over, clinica...
ObjectiveTo investigate how running, cycling, and sedentary cardiovascular stress impact biomarkers of cartilage turnover acutely in subjects with knee osteoarthritis (OA).DesignThis 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.ResultsMean 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 = -12.3%, 95% confidence interval [CI]: -19.3% to -5.2%). PRO-C2 increased during cycling (T = 14.0%, 95% CI = 4.1% to 23.8%) and running (T = 16.5%, 95% CI = 4.3% to 28.6%). T2CM decreased after cycling (T = -19.9%, 95% CI = -29.2% to -10.6%), running (T = -22.8%, 95% CI = -32.1% to -13.5%), and infusion of adrenaline (peak, T = -9.8%, 95% CI = -20.0% to 0.4%). A latent increase was seen in Coll2-1 240 minutes after running (T = 21.7%, 95% CI = -1.6% to 45.1%).ConclusionExercise 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.
Hsa_circ_0007482 Promotes Proliferation and Differentiation of Chondrocytes in Knee Osteoarthritis.
Hou D, Lu L, Tao R
Cartilage · 2026 Jun · PMID 38747467 · Full text
ObjectiveKnee osteoarthritis (KOA) is a complex degenerative joint disease and a major cause of joint dysfunction. This study aimed to explore the function of hsa_circ_0007482 on inflammation, proliferation, differentiat...
ObjectiveKnee osteoarthritis (KOA) is a complex degenerative joint disease and a major cause of joint dysfunction. This study aimed to explore the function of hsa_circ_0007482 on inflammation, proliferation, differentiation, and apoptosis in KOA.DesignReal-time quantitative polymerase chain reaction (PCR) was performed to detect the expression of circ_0007482, inflammatory factors, and differentiation-related molecules in KOA chondrocytes and interleukin (IL)-1β-stimulated chondrocytes. The correlation between the circ_0007482 expression and inflammatory factors was analyzed by the Pearson method. KOA cell model was established using IL-1β for 24 hours. The proliferation activity of chondrocytes was evaluated by CCK-8 assay, and cell apoptosis rate was assessed by flow cytometry. The downstream miRNA of circ_0007482 was validated using dual-luciferase reporter assay.ResultsThe circ_0007482 expression was elevated in both KOA cartilage tissues and IL-1β-treated chondrocytes and positively correlated with inflammatory factors expression. In comparison to the control group, IL-1β treatment diminished chondrocyte proliferation abilities and increased cell apoptosis and inflammatory factors IL-6, IL-8, and tumor necrosis factor (TNF)-α mRNA expression. Inhibition of circ_0007482 partially improved IL-1β-induced inflammatory reaction. Circ_0007482 could negatively regulate the expression of miR-558.ConclusionsInterfering of circ_0007482 might partially promote cell proliferation and differentiation, while inhibit cell apoptosis to improve joint injury by regulating miR-558 in IL-1β-treated chondrocyte cell model.
Hyaluronic Acid and Large Extracellular Vesicles (EVs) in Synovial Fluid and Plasma of Patients With End-Stage Arthritis: Positive Association of EVs to Joint Pain.
Mustonen AM, Capra J, Oikari S … +10 more , Säisänen L, Karttunen L, Julkunen P, Lehenkari P, Joukainen A, Jaroma A, Paakkonen T, Kääriäinen T, Kröger H, Nieminen P
Cartilage · 2025 Jun · PMID 38726690 · Full text
ObjectiveHyaluronic acid (HA) in synovial fluid (SF) contributes to boundary lubrication with altered levels in osteoarthritis (OA) and rheumatoid arthritis (RA). SF extracellular vesicles (EVs) may participate in arthri...
ObjectiveHyaluronic acid (HA) in synovial fluid (SF) contributes to boundary lubrication with altered levels in osteoarthritis (OA) and rheumatoid arthritis (RA). SF extracellular vesicles (EVs) may participate in arthritis by affecting inflammation and cartilage degradation. It remains unknown whether HA and EVs display joint-specific alterations in arthritic SFs.DesignWe investigated the numbers and characteristics of HA-particles and large EVs in SF from knees and shoulders of 8 OA and 8 RA patients and 8 trauma controls, and in plasma from 10 healthy controls and 11 knee OA patients. The plasma and SF HA concentrations were determined with a sandwich-type enzyme-linked sorbent assay, and EVs and HA-particles were characterized from plasma and unprocessed and centrifuged SFs with confocal microscopy. The data were compared according to diagnosis, location, and preanalytical processing.ResultsThe main findings were: (1) OA and RA SFs can be distinguished from trauma joints based on the distinctive profiles of HA-particles and large EVs, (2) there are differences in the SF HA and EV characteristics between shoulder and knee joints that could reflect their dissimilar mobility, weight-bearing, and shock absorption properties, (3) EV counts in SF and plasma can positively associate with pain parameters independent of age and body adiposity, and (4) low-speed centrifugation causes alterations in the features of HA-particles and EVs, complicating their examination in the original state.ConclusionsArthritis and anatomical location can affect the characteristics of HA-particles and large EVs that may have potential as biomarkers and effectors in joint degradation and pain.
Association Between Statin Use and the Incidence of Clinically Diagnosed Osteoarthritis: A Nationwide Retrospective Cohort Study in Taiwan.
Lin GL, Keller JJ, Wang LH
Cartilage · 2025 Sep · PMID 38726681 · Full text
ObjectiveTo investigate the effect of higher cumulative defined daily dose per year (cDDD/y) compared with lower cDDD/y of statin use in the incidence of any joint osteoarthritis (OA).DesignIn this population-based retro...
ObjectiveTo investigate the effect of higher cumulative defined daily dose per year (cDDD/y) compared with lower cDDD/y of statin use in the incidence of any joint osteoarthritis (OA).DesignIn this population-based retrospective cohort study, patients who were aged ≥40 years were newly initiated on statin therapy between 2002 and 2011, and had a statin prescription for ≥90 days in the first year of treatment were identified from the 2000 Longitudinal Generation Tracking Database. All patients were separated into groups with higher cDDD/y (>120 cDDD/y) and lower cDDD/y (≤120 cDDD/y; as an active comparator) values. Propensity score matching was performed to balance potential confounders. All recruited patients were followed up for 8 years. Marginal Cox proportional hazard models were used to estimate time-to-event outcomes of OA.ResultsCompared with lower cDDD/y use, higher cDDD/y use did not reduce the risk of any joint OA (adjusted hazard ratio, 1.07; 95% confidence interval, 0.99-1.14). Dose-related analysis did not reveal any dose-dependent association. A series of sensitivity analyses showed similar results. Joint-specific analyses revealed that statin did not reduce the incidence of knee, hand, hip, and weight-bearing (knee or hip) OA.ConclusionsHigher cDDD/y statin use did not reduce the risk of OA in this Taiwanese nationwide cohort study. The complexity of OA pathogenesis might contribute to the ineffectiveness of statin. Repurposing statin with its anti-inflammation properties might be ineffective for OA development, and balancing the catabolism and anabolism of cartilage might be a major strategy for OA prevention.
Knee Cartilage Injuries in Football Players: Clinical Outcomes and Return to Sport After Surgical Treatment: A Systematic Review of the Literature.
Andriolo L, Marín Fermín T, Chiari Gaggia GMM … +6 more , Serner A, Kon E, Papakostas E, Massey A, Verdonk P, Filardo G
Cartilage · 2025 Mar · PMID 38651797 · Full text
OBJECTIVE: To systematically review the literature and analyze clinical outcomes and return-to-sport after surgical management of cartilage injuries in football players. DESIGN: A systematic literature review was perform...
OBJECTIVE: To systematically review the literature and analyze clinical outcomes and return-to-sport after surgical management of cartilage injuries in football players. DESIGN: A systematic literature review was performed in August 2023 on PubMed, WebOfScience, and Cochrane Library to collect studies on surgical strategies for cartilage lesions in football players. Methodological quality and risk of bias were assessed with the modified Coleman Methodology score and RoB2 and RoBANS2 tools. RESULTS: Fifteen studies on 409 football players (86% men, 14% women) were included: nine prospective and two retrospective case series, one randomized controlled trial, one prospective comparative study, one case report, and one survey. Bone marrow stimulation (BMS) techniques were the most documented. The lesion size influenced the treatment choice: debridement was used for small lesions (1.1 cm), BMS, osteochondral autograft transplantation (OAT), matrix-assisted autologous chondrocytes transplantation (MACT), and scaffold-augmented BMS for small/mid-size lesions (2.2-3.0 cm), and autologous chondrocytes implantation (ACI) for larger lesions (5.8 cm). The surgical options yielded different results in terms of clinical outcome and return-to-sport, with fastest recovery for debridement and scaffold-augmented BMS. The current evidence is limited with large methodological quality variation (modified Coleman Methodology score 43.5/100) and a high risk of bias. CONCLUSIONS: Decision-making in cartilage injuries seems to privilege early return-to-sport, making debridement and microfractures the most used techniques. The lesion size influences the treatment choice. However, the current evidence is limited. Further studies are needed to confirm these findings and establish a case-based approach to treat cartilage injuries in football players based on the specific patient and lesion characteristics and the treatments' potential in terms of both return-to-sport and long-term results. LEVEL OF EVIDENCE: Systematic review, level IV.
Effect of Press-Fit Size on Insertion Mechanics and Cartilage Viability in Human and Ovine Osteochondral Grafts.
Suderman RP, Hurtig MB, Grynpas MD … +2 more , Kuzyk PRT, Changoor A
Cartilage · 2026 Jun · PMID 38651510 · Full text
ObjectiveThe osteochondral allograft procedure uses grafts constructed larger than the recipient site to stabilize the graft, in what is known as the press-fit technique. This research aims to characterize the relationsh...
ObjectiveThe osteochondral allograft procedure uses grafts constructed larger than the recipient site to stabilize the graft, in what is known as the press-fit technique. This research aims to characterize the relationships between press-fit size, insertion forces, and cell viability in ovine and human osteochondral tissue.DesignHuman (4 donors) and ovine (5 animals) articular joints were used to harvest osteochondral grafts (4.55 mm diameter, N = 33 Human, N = 35 Ovine) and create recipient sites with grafts constructed to achieve varying degrees of press fit (0.025-0.240 mm). Donor grafts were inserted into recipient sites while insertion forces were measured followed by quantification of chondrocyte viability and histological staining to evaluate the extracellular matrix.ResultsBoth human and ovine tissues exhibited similar mechanical and cellular responses to changes in press-fit. Insertion forces (Human: 3-169 MPa, Ovine: 36-314 MPa) and cell viability (Human: 16%-89% live, Ovine: 2%-76% live) were correlated to press-fit size for both human (force: = 0.539, viability: = -0.729) and ovine (force: = 0.655, viability: = -0.714) tissues. In both species, a press-fit above 0.14 mm resulted in reduced cell viability below a level acceptable for transplantation, increased insertion forces, and reduced linear correlation to press-fit size compared to samples with a press-fit below 0.14 mm.ConclusionsIncreasing press-fit size required increased insertion forces and resulted in reduced cell viability. Ovine and human osteochondral tissues responded similarly to impact insertion and varying press-fit size, providing evidence for the use of the ovine model in allograft-related research.
Intermediate-Term Clinical Outcomes of High-Density Autologous Chondrocyte Implantation in Patients with Concomitant Anterior Cruciate Ligament Reconstruction and Focal Chondral Lesions.
Guillén-Vicente I, Herros-García R, Guillén-Vicente M … +7 more , Ruiz B, Lopez-Alcorocho JM, Rodríguez-Iñigo E, Barrera A, Fernández-Jaén TF, Abelow S, Guillén-García P
Cartilage · 2025 Mar · PMID 38651496 · Full text
OBJECTIVE: To investigate intermediate-term clinical results in patients with concomitant anterior cruciate ligament (ACL) reconstruction and chondral defect treated with high-density autologous chondrocyte implantation...
OBJECTIVE: To investigate intermediate-term clinical results in patients with concomitant anterior cruciate ligament (ACL) reconstruction and chondral defect treated with high-density autologous chondrocyte implantation (HD-ACI) compared to patients without ACL tear but with a chondral lesion and HD-ACI treatment. DESIGN: Forty-eight patients with focal chondral lesions underwent HD-ACI (24 with ACL reconstruction after an ACL injury and 24 with an intact ACL). Follow-up assessments occurred at 6, 12, and 24 months. Patient-reported knee function and symptoms were assessed using the International Knee Documentation Committee (IKDC) questionnaire, pain was measured using the Visual Analog Scale (VAS), and adverse events were monitored. Physical activity was assessed using the Tegner Activity Level Scale, and cartilage healing was evaluated with the Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score. RESULTS: No significant adverse events occurred during follow-up. Both groups showed significant improvements at 2 years compared to baseline (VAS: 8.0 ± 1.3 to 1.4 ± 2.0 [normal ACL]; 7.4 ± 2.3 to 2.1 ± 2.3 [ACL reconstruction]; IKDC: 39.2 ± 10.6 to 76.1 ± 22.0 [intact ACL]; 35.6 ± 12.1 to 74.6 ± 20.9 [ACL reconstruction]). Patients in both groups exceeded the minimal clinically important difference (MCID) for IKDC scores. The Tegner Activity Level Scale decreased immediately after surgery and increased after 2 years, with 70.6% (normal ACL) and 89.5% (ACL reconstruction) returning to their preinjury activity levels. No significant differences in the MOCART score were observed between the groups. CONCLUSIONS: ACL reconstruction does not appear to reduce the outcomes (at 2 years) of HD-ACI.
BMSC-Derived Exosomes Attenuate Rat Osteoarthritis by Regulating Macrophage Polarization through PINK1/Parkin Signaling Pathway.
Li B, Shen E, Wu Z … +4 more , Qi H, Wu C, Liu D, Jiang X
Cartilage · 2026 Jun · PMID 38641989 · Full text
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...
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 and the OA rats .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.
The Interplay Between Endoplasmic Reticulum Stress and Oxidative Stress in Chondrocyte Catabolism.
Kim YJ, Han J, Han S
Cartilage · 2026 Jun · PMID 38641979 · Full text
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 contrib...
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 .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.
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.
Chua SKK, Wong WS, Koh DTS … +4 more , Sultana R, Soong J, Lee KH, Bin Abd Razak HR
Cartilage · 2025 Mar · PMID 38624072 · Full text
OBJECTIVE: The 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...
OBJECTIVE: The 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. METHODS: A 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. RESULTS: Significantly 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 ( < 0.05). No significant difference in complications rates was noted between the two groups at 1 year. CONCLUSIONS: Bone 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).
Expression of Chondrogenic Potential Markers in Cultured Chondrocytes from the Human Knee Joint.
Bonello JP, Tse MY, Robinson TJG … +3 more , Bardana DD, Waldman SD, Pang SC
Cartilage · 2025 Dec · PMID 38616342 · Full text
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 cul...
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.
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.
Retzky JS, Fletcher C, Rizy M … +2 more , Burge A, Strickland SM
Cartilage · 2025 Mar · PMID 38613220 · Full text
PURPOSE: The 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 i...
PURPOSE: The 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. METHODS: Patients 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 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). RESULTS: Thirty-four patients were included, with a median age of 35.1 years [IQR: 24.6, 37.1], and BMI of 24.0 kg/m [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, = 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). CONCLUSION: Higher 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.
Significant Clinical Improvement After Arthroscopic Autologous Matrix-Induced Chondrogenesis for Osteochondral Lesions of the Talus: A 5-Year Follow-Up.
Efrima B, Barbero A, Maccario C … +5 more , Indino C, Nocera C, Albagli A, Dahmen J, Usuelli FG
Cartilage · 2026 Mar · PMID 38554040 · Full text
PurposeThis 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 seconda...
PurposeThis 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.DesignSixty-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 and over 1.5 cm). The effect of each category was evaluated.ResultsThere were significant improvements in the VAS, AOFAS, SF-12, and UCLA, comparing the preoperative scores to the 60-month follow-up scores ( < 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 ( = 0.005, 0.004, and <0.001, respectively). Overweight patients had lower VAS, SF-12, Halasi, and UCLA scores ( = 0.006, 0.002, 0.024, and 0.007, respectively). Lesion size was uninfluential.ConclusionA-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.
Intra-Articular Injection of Interleukin-8 Neutralizing Monoclonal Antibody Effectively Attenuates Osteoarthritis Progression in Rabbits.
Yang J, Wang X, Zhang Y … +11 more , He R, Fu Z, Wang R, Ma Y, Fu D, Meng S, Cai W, Zhou Y, Chen C, Chen G, Gong X
Cartilage · 2025 Dec · PMID 38525935 · Full text
ObjectiveCytokines 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.DesignThe study...
ObjectiveCytokines 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.DesignThe 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.ResultsCompared 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.ConclusionsThe 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.
Evidence-Based Update on the Surgical Technique and Clinical Outcomes of Retrograde Drilling: A Systematic Review.
Yasui Y, Miyamoto W, Shimozono Y … +3 more , Tsukada K, Kawano H, Takao M
Cartilage · 2026 Mar · PMID 38506486 · Full text
BackgroundRetrograde 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 formati...
BackgroundRetrograde 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.DesignA 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.ResultsEleven 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.ConclusionsThis 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.
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.
Gaissmaier C, Angele P, Spiro RC … +3 more , Köhler A, Kirner A, Niemeyer P
Cartilage · 2025 Jun · PMID 38501741 · Full text
ObjectiveTo 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.Desig...
ObjectiveTo 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.DesignPropensity 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.ResultsGroups 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 vs. 3.7 cm). 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%; = 0.0108), symptoms (84.7% vs. 61.1%, = 0.0039), sports/recreation (84.7% vs. 56.9%, = 0.0008), and quality of life (QoL; 72.2% vs. 44.4%, = 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).ConclusionHydrogel-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.
The BMP7-Derived Peptide p[63-82] Reduces Cartilage Degeneration in the Rat ACLT-pMMx Model for Posttraumatic Osteoarthritis.
Ripmeester EGJ, Steijns JSJJ, Wijnands KAP … +13 more , Stassen RHMJ, Pitelka V, Peeters LCW, Cremers A, Astryde NMSA, Chabronova A, Surtel DAM, Emans PJ, van den Akker GGH, van Rietbergen B, van Rhijn LW, Caron MMJ, Welting TJM
Cartilage · 2025 Dec · PMID 38501739 · Full text
ObjectiveOsteoarthritis (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 pr...
ObjectiveOsteoarthritis (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.DesignSkeletally 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.ResultsHistopathological 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.ConclusionsWeekly 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.
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