BMSC Derived Exosomes Attenuate Apoptosis of Temporomandibular Joint Disc Chondrocytes in TMJOA via PI3K/AKT Pathway.

Abstract

Bone marrow mesenchymal stem cell-derived exosomes (BMSC-Exos) are crucial means of intercellular communication and can regulate a range of biological processes by reducing inflammation, decreasing apoptosis and promoting tissue repair. We treated temporomandibular joint (TMJ) disc chondrocytes with TNF-α and performed local injection of sodium iodoacetate (MIA) in the TMJ of rats to establish in vitro and in vivo models of TMJ osteoarthritis (TMJOA). BMSC-Exos were isolated and extracted to evaluate their proliferation and trilineage differentiation abilities, and their antiapoptotic and chondroprotective effects were assessed. This study revealed that BMSC-Exos can be endocytosed by TMJ disc chondrocytes in vitro and that BMSC-Exos pretreatment strongly attenuated the inhibitory effect of TNF-α on the proliferative and chondrogenic potential of TMJ disc chondrocytes. The administration of BMSC-Exos significantly suppressed TNF-α-induced apoptosis in TMJ disc chondrocytes by increasing the phosphorylation level of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB/AKT) pathway-related proteins, whereas the PI3K inhibitor LY294002 neutralized this antiapoptotic effect. Intradiscal injection of BMSC-Exos alleviated the degeneration and inflammation of TMJ discs in a rat model of TMJOA. Our study revealed that BMSC-Exos can attenuate the apoptosis of TMJ disc chondrocytes and destruction of TMJ discs partially by inhibiting the apoptotic pathway and activating the PI3K/AKT pathway, thereby providing a promising treatment strategy for the regeneration of damaged TMJ discs.