In this study, we examined the relationship between time-course changes in the numbers of SF-MSCs and the histological changes in knee joint tissues in a rat OA model. Another unanswered question is whether endogenous SF-MSCs undergo tissue destructive or reparative phenotype changes in response to the inflammatory and catabolic environment associated with OA. However, the mechanism by which the numbers of SF-MSCs change with OA progression and the nature of the structural changes of the joint that are predominantly associated with the changes in SF-MSC numbers remain unclear. A better understanding of how endogenous SF-MSCs are mobilized could therefore lead to the development of novel OA therapies that would not require the injection of exogenous MSCs.Ī previous study revealed changes in the number and gene expression signature of SF-MSCs from OA patients before and after knee joint distraction surgery. These findings suggest that SF-MSCs naturally originate in the synovium and contribute to the endogenous repair of damaged intra-articular tissues. also showed that SF-MSCs immediately adhered to the surface of degenerated cartilage following intra-articular injection in a canine OA model. We previously reported the in vitro release of SF-MSCs from OA synovium and that the released SF-MSCs have gene expression profiles and therapeutic potentials comparable to those of synovial MSCs. Although synovial fluid MSCs (SF-MSCs) are seldom observed in healthy knees, their numbers increase in OA knees and in knees with injuries to the meniscus or anterior cruciate ligament. MSCs exist in the synovium, but they are also present in synovial fluid (SF). We have previously confirmed that the intra-articular injection of autologous synovial MSCs into the knees of patients with OA can improve their pain scores and the volume of articular cartilage. These cells reside in various tissues, but synovial MSCs are the most promising cell types for cartilage regeneration because they are committed to a chondrogenic lineage. MSCs have self-renewal and chondrogenic abilities and secrete abundant immunomodulatory/trophic factors in vivo. One of the most attractive OA solutions is the intra-articular injection of mesenchymal stem cells (MSCs). Therefore, many researchers have devoted significant effort toward developing new OA treatments. Some treatment options can reduce OA pain, but no cures or disease-modifying drugs are presently available. OA is characterized by progressive cartilage destruction, meniscus degeneration, subchondral bone sclerosis, and synovitis. Osteoarthritis (OA) of the knee, which affects approximately 250 million people worldwide, is a very serious and increasing cause of disability. Tissue-reparative gene expression patterns were observed in SF-MSCs from OA knees, but not from knees without intra-articular tissue damage. The number of SF-MSCs was most closely correlated with the severity of synovitis in this rat OA model. 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. Synovitis scores showed the strongest correlation with colony numbers ( R = 0.583) and areas ( R = 0.456). ResultsĬolony-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. RNA sequencing was performed for SF-MSCs from intact knees and knees 4 weeks after the pMx and sham surgery. Joint structural changes were evaluated histologically to investigate their correlation with the numbers and areas of colonies. SF was cultured for 1 week to calculate the numbers of colony-forming cells and colony areas. SF and knee joints were collected from intact rats and from rats at 2, 4, and 6 weeks after surgery. Partial medial meniscectomy (pMx) and sham surgery were performed on both knees of rats. 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. Synovial fluid mesenchymal stem cells (SF-MSCs) originate in the synovium and contribute to the endogenous repair of damaged intra-articular tissues.
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