Abstract
Osteoarthritis (OA) is a degenerative disease that causes chronic pain and disability worldwide. This disease is mainly caused by IL-1β and TNF-α, which lead to cartilage degradation and inhibit the repair capacity of damaged cartilage. Recent studies have shown that amniotic fluid mesenchymal stem cells (AF-MSCs) secrete proteins that can effectively help in the treatment of cartilage damaged by OA. However, the underlying mechanism is still unclear. Therefore, the aim of this study was to investigate the effects and mechanisms behind the healing properties of the AF-MSC secretome (AFS-se) under OA conditions. This study involved growing chondrocyte progenitor cells (CPCs) and traumatized cartilage tissues in the presence of the cytokines IL-1β and TNF-α, which mimic OA conditions. AFS-se was then added to the culture medium to determine its effect on the CPCs and cartilage. Cell migration, endogenous cell outgrowth, the expression of chondrogenic and anabolic genes, and the mechanism of proteins in the NF-κB and MAPK signaling pathways were examined in this study. AFS-se inhibited the inflammatory effects of IL-1β and TNF-α by significantly reducing ERK phosphorylation in the MAPK signaling pathway and decreasing downstream proinflammatory COX2 products. The impaired CPCs recovered their ability to migrate, and endogenous CPCs in injured osteoarthritic cartilage were able to regrow in response to inflammatory stimuli. Additionally, the expression of anabolic genes such as Col I, Col II, and IGF1 was restored in defective CPCs. In conclusion, this study demonstrated that AFS-se has therapeutic effects on OA by inhibiting the inflammatory functions of IL-1β and TNF-α through protein phosphorylation in the MAPK pathway while also promoting the regenerative and self-repair functions of CPCs in traumatized cartilage.