Cartilage progenitor cells derived extracellular vesicles-based cell-free strategy for osteoarthritis treatment by efficient inflammation inhibition and extracellular matrix homeostasis restoration.

Osteoarthritis (OA) is a common degenerative joint disease which currently lacks of effective agents. It is therefore urgent and necessary to seek an effective approach that can inhibit inflammation and promote cartilage matrix homeostasis. Cartilage progenitor cells (CPCs) are identified as a cell population of superficial zone in articular cartilage which possess strong migration ability, proliferative capacity, and chondrogenic potential. Recently, the application of CPCs may represent a novel cell therapy strategy for OA treatment. There is growing evidence that extracellular vesicles (EVs) are primary mediators of the benefits of stem cell-based therapy. In this study, we explored the protective effects of CPCs-derived EVs (CPCs-EVs) on IL-1ß-induced chondrocytes. We found CPCs-EVs exhibited chondro-protective effects in vitro. Furthermore, our study demonstrated that CPCs-EVs promoted matrix anabolism and inhibited inflammatory response at least partially via blocking STAT3 activation. In addition, liquid chromatography-tandem mass spectrometry analysis identified 991 proteins encapsulated in CPCs-EVs. By bioinformatics analysis, we showed that STAT3 regulatory proteins were enriched in CPCs-EVs and could be transported to chondrocytes. To promoting the protective function of CPCs-EVs in vivo, CPCs-EVs were modified with cationic peptide ε-polylysine-polyethylene-distearyl phosphatidylethanolamine (PPD) for surface charge reverse. In posttraumatic OA mice, our results showed PPD modified CPCs-EVs (PPD-EVs) effectively inhibited extracellular matrix catabolism and attenuated cartilage degeneration. Moreover, PPD-EVs down-regulated inflammatory factors expressions and reduced OA-related pain in OA mice. In ex-vivo cultured OA cartilage explants, PPD-EVs successfully promoted matrix anabolism and inhibited inflammation. Collectively, CPCs-EVs-based cell-free therapy is a promising strategy for OA treatment.

Incidence and Characteristics of Knee Ligament and Meniscal Injuries in Patients With Posterolateral Tibial Plateau Fractures.

Background: Anterior cruciate ligament (ACL) tears are commonly seen with concomitant injuries to the posterolateral tibial plateau, while the occurrence of ACL injuries in posterolateral tibial plateau fractures (PTPFs) remains unclear. Purpose: To (1) explore the incidence of knee ligament (anterior or posterior cruciate ligament, medial or lateral collateral ligament) and medial or lateral meniscus injuries in patients with PTPF and (2) find reliable PTPF-related parameters to predict the risk of knee ligament and meniscal injuries. Study Design: Cross-sectional study; Level of evidence, 3. Methods: Patients diagnosed with PTPF who had computed tomography and magnetic resonance imaging (MRI) data were identified. Morphological parameters of the PTPF were measured on sagittal computed tomography images. Knee ligament and meniscal injuries were assessed using MRI. The association of ACL injuries with meniscal injuries was analyzed. Receiver operating characteristic (ROC) analysis was used to determine the value and cutoff point of the PTPF morphological parameters for diagnosing complete in-substance ACL tears. Results: Overall, 113 patients with PTPF were included. ACL injuries were present in 94 (83.2%) patients, including 43 (38.1%) avulsion fractures and 28 (24.8%) complete in-substance tears. Patients with in-substance ACL tears had a higher incidence of lateral meniscus posterior horn tears compared with the other patients (PBonferroni < .001). ROC analysis revealed that both the fracture depression angle (cutoff point, 25.5°) and the posterior articular surface loss percentage (cutoff point, 37.5%) had a sensitivity >90% and a specificity >80% for the diagnosis of complete in-substance ACL tears. Conclusion: ACL injuries were seen in 83.2% of the study patients. Complete in-substance ACL tears were associated with an increased incidence of lateral meniscus posterior horn tears. Among PTPF parameters, fracture depression angle and posterior articular surface loss percentage showed a high predictive value for the presence of complete in-substance ACL tears, thereby reducing delays in diagnosis and treatment.