Conditioned medium of infrapatellar fat stem cells alleviates degradation of chondrocyte extracellular matrix and delays development of osteoarthritis.

Abstract

Osteoarthritis (OA) is a common clinical chronic degenerative disease characteriszed by articular cartilage degeneration. Mesenchymal stem cells (MSCs) delay OA the development of OA mainly through paracrine effects. The conditioned medium (CM) of MSCs contains all the paracrine components of these cells, and many studies have demonstrated the anti-apoptotic and anti-inflammatory effects of CM in vitro. In this study, we investigated the effect of the CM of infrapatellar fat pad-derived MSCs (IPFSCs) on OA in vitro and in vivo, as well as and the potential underlying mechanisms. The results showed that injection of CM into the knee joint inhibited OA development in a rat model induced by destabilisation of the medial meniscus and anterior cruciate ligament transection. The CM increased the deposition of extracellular matrix-related components (type II collagen and Proteoglycan).In addition, CM inhibited the excessive production of pro-inflammatory mediators in human chondrocytes induced by IL-1 β, including COX2, iNOS, TNF- α and IL-6, and reduced the production of MMP13 and ADAMTS5, thus protecting the degradation of extracellular matrix. The activation of PI3K/AKT/NF- κ B signalling pathway was induced by IL-1β in chondrocytes, which was finally inhibited by CM-IPFSCs treatment. In summary, IPFSC-CM may have therapeutic potential for OA.