Exosomes Derived from Bone Marrow Mesenchymal Stem Cells Prevent Acidic pH-Induced Damage in Human Nucleus Pulposus Cells
Ming Li, Ruoyu Li, Sidong Yang, Dalong Yang, Xianda Gao, Jia-yuan Sun, Wenyuan Ding, Lei Ma
Abstract
BACKGROUND The exosomes (Exo) derived from mesenchymal stem cells (MSCs) are capable of attenuating the apoptosis of nucleus pulposus cells (NPCs) elicited by proinflammatory cytokines. However, it remains unknown whether MSC-derived Exo also exert a protective effect on NPCs in the pathological acid environment. MATERIAL AND METHODS NPCs were divided into 3 groups: Group A, pH 7.1-7.3; Group B, pH 6.5-6.7 and Group C, pH 5.9-6.1. The NPCs were cultured in the above-defined acidic medium, and 3 different amounts of Exo were added into the media. Finally, the expression of the caspase-3, aggrecan, collagen II, and MMP-13 was analyzed and compared among the different groups. RESULTS Compared with cells cultured at pH 7.1-7.3 (Group A), proliferation activity of NPCs cultured at pH 5.9-6.7 (Group B and C) decreased significantly. Collagen II and aggrecan expression was also obviously reduced with the decrease of cell proliferation. Conversely, the expression of caspase-3 and MMP-13 significantly increased. Further experiments showed that proliferation activity was significantly attenuated in NPCs cultured at pH 5.9-6.1 without Exo treatment (Group E) compared with those cultured at pH 7.1-7.3 without Exo treatment (Group D). CONCLUSIONS In the pathological acid environment, MSC-derived Exo promotes the expression of chondrocyte extracellular matrix, collagen II, and aggrecan, and reduces matrix degradation by downregulating matrix-degrading enzymes, protecting NPCs from acidic pH-induced apoptosis. This study reveals a promising strategy for treatment of IVD degeneration.