1. Academic Validation
  2. Icariin protects rabbit BMSCs against OGD-induced apoptosis by inhibiting ERs-mediated autophagy via MAPK signaling pathway

Icariin protects rabbit BMSCs against OGD-induced apoptosis by inhibiting ERs-mediated autophagy via MAPK signaling pathway

  • Life Sci. 2020 Jul 15;253:117730. doi: 10.1016/j.lfs.2020.117730.
Donghua Liu 1 Wang Tang 2 Hongyi Zhang 3 He Huang 1 Zhaofei Zhang 1 Dongming Tang 3 Feng Jiao 4
Affiliations

Affiliations

  • 1 Spinal Surgery, Guangzhou Hospital of Integrated Traditional and Western Medicine, Guangzhou, Guangdong, China.
  • 2 Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China.
  • 3 Joint Surgery, Guangzhou Hospital of Integrated Traditional and Western Medicine, Guangzhou, Guangdong, China.
  • 4 Joint Surgery, Guangzhou Hospital of Integrated Traditional and Western Medicine, Guangzhou, Guangdong, China. Electronic address: [email protected].
Abstract

Stem cell therapy is widely employed in treating osteoarthritis (OA), and bone marrow-derived mesenchymal stem cells (BMSCs) has gradually become the most attractive new method for treating OA due to the benefit for cartilage tissue repair. However, the Apoptosis in the neural stem cell transplantation severely decreases repairing efficacy. Icariin has been reported to exert multiple effects on BMSCs, including its proliferation, osteogenic, and chondrogenic differentiation. However, its effects on the injury induced by oxygen, glucose and serum deprivation (OGD) remains unknown. We prospectively investigated the role of ICA on rabbit BMSCs under conditions of OGD. Firstly, BMSCs were cultured under conditions of OGD, ICA relieved OGD-induced cell damage by promoting cell proliferation and suppressing Apoptosis. Secondly, Markers of endoplasmic reticulum stress (ERs), ER stress IRE-1 pathway, and Autophagy were both inhibited by ICA via inhibition of phosphor-extracellular regulated protein kinases (p-ERKs), p-P38, p-c-Jun N-terminal kinase (p-JNK) or si-MAPK. Finally, decrease of ERs marker levels enhanced protective effect of ICA against OGD-induced injury by limiting Apoptosis and Autophagy. Moreover, an Autophagy Inhibitor (3-methyladenine: 3-MA) contributed to a synergistic effect in conjunction with ICA, in promoting cell proliferation, suggesting that ICA exerts anti-ERs and anti-autophagy effects in OGD-treated BMSCs. Therefore, ICA protected rabbit BMSCs from OGD-induced Apoptosis through inhibitory regulation of ERs-mediated Autophagy related to the MAPK signaling pathway, which provided insights for a potential therapeutic strategy in OA.

Keywords

Apoptosis; Autophagy; Bone marrow-derived mesenchymal stem cells; Endoplasmic reticulum stress; Icariin; Osteoarthritis; Oxygen–glucose deprivation.

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