Background: Arthroscopic microfracture is considered the primary treatment strategy for osteochondral lesions of the talus and has been shown to provide successful outcomes. However, deterioration of clinical outcomes and fibrocartilage infill over time is now a recognized concern. The purpose of the present study was to evaluate the outcomes related to cartilage repair tissue after microfracture with use of second-look arthroscopy and magnetic resonance imaging (MRI) and to compare these findings with functional outcomes. Methods: Twenty-five patients underwent second-look arthroscopy and MRI at a mean of 3.6 years (range, 2.2 to 8.1 years) after microfracture. Second-look arthroscopic findings were assessed according to the system of the International Cartilage Repair Society (ICRS). MRI was evaluated postoperatively with use of the magnetic resonance observation of cartilage repair tissue (MOCART) score. Clinical outcomes were determined with use of the Foot and Ankle Outcome Score (FAOS), the American Orthopaedic Foot & Ankle Society (AOFAS) ankle-hindfoot scale, and the Short Form-36 (SF-36) score. Results: On second-look arthroscopy, 9 ankles (36%) were still abnormal according to the ICRS overall repair grades. The average postoperative MOCART score was 67.8 (range, 30 to 95), with good association with functional outcome. In addition, 6 patients (24%) had a mismatch between the MRI and second-look arthroscopic findings. Significant improvements were observed in all functional outcome categories between the preoperative and latest follow-up evaluations (p < 0.001). The mean FAOS scores for ICRS repair grades I and II (n = 16) and grades III and IV (n = 9) were 86.8 and 75.6, respectively. There was a significant correlation between FAOS scores and ICRS grades (p = 0.004). Conclusions: Second-look arthroscopic results revealed that 36% of lesions were incompletely healed and had inferior quality of repair tissue compared with that of native cartilage at a mean of 3.6 years, although arthroscopic microfracture provided functional improvements. Magnetic resonance analysis demonstrated some limitations in comparison with arthroscopy for the evaluation of cartilage repair. Therefore, second-look arthroscopy has an important role in accurately assessing the status of the cartilage repair tissue beyond the use of the MOCART score and functional outcomes. Level of Evidence: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Yang HY, et al. Clin Orthop Surg. 2024 Jun;16(3):422-429. https://doi.org/10.4055/cios23250

Osteoarthritis (OA) is characterized by degeneration of the joint cartilage, inflammation, and a change in the chondrocyte phenotype. Inflammation also promotes cell hypertrophy in human articular chondrocytes (HC-a) by activating the NF-κB pathway. Chondrocyte hypertrophy and inflammation promote extracellular matrix degradation (ECM). Chondrocytes depend on Smad signaling to control and regulate cell hypertrophy as well as to maintain the ECM. The involvement of these two pathways is crucial for preserving the homeostasis of articular cartilage. In recent years, Polynucleotides Highly Purified Technology (PN-HPT) has emerged as a promising area of research for the treatment of OA. PN-HPT involves the use of polynucleotide-based agents with controlled natural origins and high purification levels. In this study, we focused on evaluating the efficacy of a specific polynucleotide sodium agent, known as CONJURAN, which is derived from fish sperm. Polynucleotides (PN), which are physiologically present in the matrix and function as water-soluble nucleic acids with a gel-like property, have been used to treat patients with OA. However, the specific mechanisms underlying the effect remain unclear. Therefore, we investigated the effect of PN in an OA cell model in which HC-a cells were stimulated with interleukin−1β (IL−1β) with or without PN treatment. The CCK-8 assay was used to assess the cytotoxic effects of PN. Furthermore, the enzyme-linked immunosorbent assay was utilized to detect MMP13 levels, and the nitric oxide assay was utilized to determine the effect of PN on inflammation. The anti-inflammatory effects of PN and related mechanisms were investigated using quantitative PCR, Western blot analysis, and immunofluorescence to examine and analyze relative markers. PN inhibited IL−1β induced destruction of genes and proteins by downregulating the expression of MMP3, MMP13, iNOS, and COX-2 while increasing the expression of aggrecan (ACAN) and collagen II (COL2A1). This study demonstrates, for the first time, that PN exerted anti-inflammatory effects by partially inhibiting the NF-κB pathway and increasing the Smad2/3 pathway. Based on our findings, PN can potentially serve as a treatment for OA.

Aims: To determine the relationship between articular cartilage status and clinical outcomes after medial opening-wedge high tibial osteotomy (MOHTO) for medial compartmental knee osteoarthritis at intermediate follow-up. Methods: We reviewed 155 patients (155 knees) who underwent MOHTO from January 2008 to December 2016 followed by second-look arthroscopy with a mean 5.3-year follow-up (2.0 to 11.7). Arthroscopic findings were assessed according to the International Cartilage Repair Society (ICRS) Cartilage Repair Assessment (CRA) grading system. Patients were divided into two groups based on the presence of normal or nearly normal quality cartilage in the medial femoral condyle: good (second-look arthroscopic) status (ICRS grade I or II; n = 70), and poor (second-look arthroscopic) status (ICRS grade III or IV; n = 85) groups at the time of second-look arthroscopy. Clinical outcomes were assessed using the International Knee Documentation Committee (IKDC) score, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and 36-Item Short Form survey. Results: Significant improvements in all clinical outcome categories were found between the preoperative and second-look arthroscopic assessments in both groups (p < 0.001). At the latest follow-up, the mean IKDC and WOMAC scores in the good status group further improved compared with those at the time of second-look arthroscopic surgery (p < 0.001), which was not shown in the poor status group. The mean IKDC (good status, 72.8 (SD 12.5); poor status, 64.7 (SD 12.1); p = 0.002) and mean WOMAC scores (good status, 15.7 (SD 10.8); poor status, 21.8 (SD 13.6); p = 0.004) significantly differed between both groups at the latest follow-up. Moreover, significant correlations were observed between ICRS CRA grades and IKDC scores (negative correlation; p < 0.001) and WOMAC scores (positive correlation; p < 0.001) at the latest follow-up. Good cartilage status was found more frequently in knees with the desired range of 2° to 6° valgus correction than in those with corrections outside this range (p = 0.019). Conclusion: Second-look arthroscopic cartilage status correlated with clinical outcomes after MOHTO at intermediate-term follow-up, despite the relatively small clinical differences between groups. Cite this article: Bone Joint J 2021;103-B(11):1686–1694.

Osteoarthritis (OA) is a prevalent and debilitating joint disorder that affects a substantial proportion of the global population, underscoring the urgent need for therapeutic strategies that extend beyond symptomatic management. Although mesenchymal stem cells (MSCs) have emerged as a promising therapeutic modality, their clinical application remains constrained by several inherent limitations. This study explores a cell-free alternative by investigating the therapeutic potential of exosomes derived from bone marrow (BMSCs), adipose tissue (ADSCs), and umbilical cord (UMSCs) MSCs in mitigating OA pathogenesis, utilizing both in vitro and ex vivo models. Exosomes from each MSC source were isolated and characterized through nanoparticle tracking analysis, transmission electron microscopy, and Western blotting to confirm their identity and purity. Subsequently, their chondroprotective, anti-inflammatory, and regenerative properties were systematically assessed through evaluations of cell viability, expression profiles of inflammatory and chondroprotective markers, and chondrocyte migration assays. The results demonstrate that all three types of MSC-derived exosomes (MSC-Exos) exhibit low cytotoxicity while significantly suppressing proinflammatory markers and enhancing the expression of chondroprotective genes. Notably, BMSC-Exos and UMSC-Exos displayed superior efficacy in attenuating inflammation, promoting cartilage protection, and inhibiting chondrocyte apoptosis. Furthermore, all MSC-Exos markedly enhanced chondrocyte motility, a critical component of cartilage repair. Collectively, these findings support the therapeutic promise of MSC-Exos, particularly those derived from BMSCs and UMSCs, as a targeted, cell-free approach for the treatment of OA compared to ADSCs. By modulating inflammation, promoting cartilage regeneration, and preventing chondrocyte apoptosis, MSC-Exos may serve as a viable and scalable alternative to current MSC-based therapies for this widespread degenerative disease.

Background: The relationship between preoperative subchondral bone marrow edema (BME) in the osteoarthritic knee and pain has been established. However, little is known about the influence of preoperative BME on outcomes after medial opening-wedge high tibial osteotomy (MOHTO). The purpose of this study was to clarify the association between preoperative BME severity and clinical outcomes after MOHTO at intermediate follow-up. Methods: We reviewed the cases of 105 consecutive patients who underwent MOHTO for osteoarthritis of the knee with preoperative subchondral BME in the medial aspect of the tibia between January 2005 and December 2015. BME was evaluated using magnetic resonance imaging (MRI). The sizes of the BME lesions were determined on the basis of the maximum diameter and were classified as small (<1 cm), medium (<2 cm), large (4 cm). Associations between preoperative BME severity and postoperative outcomes at a mean follow-up of 6.2 years (range, 2.0 to 14.3 years) were evaluated according to a Spearman correlation matrix with each reviewer’s grades. Functional outcomes were assessed using the Hospital for Special Surgery (HSS) score, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Knee Society Score (KSS), and Short Form-12 (SF-12) questionnaire. Survival rate and complications were also evaluated. Results: The degree of preoperative BME was not significantly correlated with postoperative outcomes (p > 0.05). There were significant improvements between the preoperative and latest follow-up assessments in all functional outcome categories (p < 0.001). Patients demonstrated marked improvements with respect to pain, function, and quality of life. The overall survival rate was 95.2%, with a mean follow-up of 6.2 years. Six major complications were identified in 5.7% of the patients, and these resulted in 5 patients (4.8%) who had conversion to total knee arthroplasty. Conclusions: We did not find any correlation between preoperative subchondral BME severity and postoperative outcomes. MOHTO showed good functional outcomes, a low major complication rate, and an excellent survival rate with a mean follow-up of 6.2 years, regardless of the degree of preoperative BME. Level of Evidence: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.