Mesenchymal stem cells in synovial fluid increase in number in response to synovitis and display more tissue-reparative phenotypes in osteoarthritis

<jats:title>Abstract</jats:title> <jats:sec> <jats:title>Background</jats:title> <jats:p>Synovial fluid mesenchymal stem cells (SF-MSCs) originate in the synovium and contribute to the endogenous repair of damaged intra-articular tissues. Here, we clarified the relationship between their numbers and joint structural changes during osteoarthritis (OA) progression and investigated whether SF-MSCs had phenotypes favorable for tissue repair, even in an OA environment.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>Partial medial meniscectomy (pMx) and sham surgery were performed on both knees of rats. SF and knee joints were collected from intact rats and from rats at 2, 4, and 6 weeks after surgery. SF was cultured for 1 week to calculate the numbers of colony-forming cells and colony areas. Joint structural changes were evaluated histologically to investigate their correlation with the numbers and areas of colonies. RNA sequencing was performed for SF-MSCs from intact knees and knees 4 weeks after the pMx and sham surgery.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p> Colony-forming cell numbers and colony areas were greater in the pMx group than in the intact and sham groups and peaked at 2 and 4 weeks, respectively. Synovitis scores showed the strongest correlation with colony numbers ( <jats:italic>R</jats:italic>  = 0.583) and areas ( <jats:italic>R</jats:italic>  = 0.456). RNA sequencing revealed higher expression of genes related to extracellular matrix binding, TGF-β signaling, and superoxide dismutase activity in SF-MSCs in the pMx group than in the sham group. </jats:p> </jats:sec> <jats:sec> <jats:title>Conclusion</jats:title> <jats:p>The number of SF-MSCs was most closely correlated with the severity of synovitis in this rat OA model. Tissue-reparative gene expression patterns were observed in SF-MSCs from OA knees, but not from knees without intra-articular tissue damage.</jats:p> </jats:sec>