Altered function in cartilage derived mesenchymal stem cell leads to OA-related cartilage erosion.

A portion of osteoarthritis (OA) patients with total knee arthroplasty (TKA) had monocondylar destruction in medial femoral condyle, but healthy-appearant cartilage in lateral side. However, there is limited information concerning functional differences of cartilage derived mesenchymal stem cell (CMSC) between these two locations in the same donor and its possible role in the pathogenesis of OA. Cells isolated from the degraded cartilage in medial condyle and normal cartilage in lateral side from OA patients were identified with co-expressed markers CD105 and CD166 and confirmed as CMSCs by immunophenotype. The relative percentage, proliferation activity, multi-lineage differentiation potential and miRNA expression profile of CMSCs in two groups were compared by flow cytometry, CCK-8 assay, cytochemical staining, immunohistochemistry, real-time PCR and miRNA microarray analysis. Our study suggested that the percentage (10.61±6.97% vs. 18.44±9.97%, P<0.05) and proliferation rate (P<0.01) of CD105+/CD166+ CMSCs from the degraded cartilage were significantly reduced compared with those from the normal cartilage. CMSCs from the degraded cartilage also showed stronger osteogenic (P<0.05), weaker adipogenic (P<0.01), and comparable chondrogenic potential (P>0.05) during differentiation. MiR-31-5p and miR-424-5p were down regulated in CMSCs from the degraded cartilage. In conclusion, altered function such as reduced percentage and proliferation ability, as well as changes in differentiation profile of CMSC contributed to homeostasis imbalance, leading to OA-related cartilage erosion. Furthermore, regulatory networks of multiple miRNAs may be partially responsible for the dysfunction of CMSCs.