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The miRNA-15b/USP7/KDM6B axis engages in the initiation of osteoporosis by modulating osteoblast differentiation and autophagy |
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| Authors: | Xiaohui Lu Yuantao Zhang Yin Zheng Bin Chen |
| Affiliation: | 1. Department of Orthopedics, The First Affiliated Hospital of Shantou University Medical College, Shantou, China Contribution: Conceptualization (equal), Writing - original draft (equal), Writing - review & editing (equal);2. Department of Orthopedics, The First Affiliated Hospital of Shantou University Medical College, Shantou, China Contribution: Conceptualization (equal), Data curation (equal), Formal analysis (equal), Methodology (equal), Resources (equal), Software (equal), Writing - review & editing (equal);3. Department of Teaching and Research, The First Affiliated Hospital of Shantou University Medical College, Shantou, China Contribution: Conceptualization (equal), Writing - original draft (equal), Writing - review & editing (equal);4. Department of Orthopedics, The First Affiliated Hospital of Shantou University Medical College, Shantou, China |
| Abstract: | Osteoporosis is a metabolic disease that results from oxidative stress or inflammation in renal disorders. microRNAs (miRNAs) are recently implicated to participate in osteoporosis, but the mechanism remains largely unexplored. Herein, we aimed to explore the potential role of miR-15b in osteoblast differentiation and autophagy in osteoporosis. We established osteoporosis models through ovariectomy and determined that miR-15b was highly expressed whereas USP7 and KDM6B were poorly expressed in tissue of osteoporosis mice. Treatment of silenced miR-15b resulted in the elevation of decreased bone mineral density (BMD), the maximum elastic stress and the maximum load of osteoporosis mice. In osteoblasts, miR-15 overexpression decreased proliferation but suppressed the cell differentiation and autophagy, accompanied with decreased expression of USP7. Mechanistically, miR-15 bound and inhibited USP7 expression, while overexpression of USP7 promoted autophagy of osteoblasts. USP7, importantly, strengthened the stability of KDM6B and promoted KDM6B expression. MG132 protease inhibitor increased KDM6B and USP7 expression in osteoblasts. Silencing of KDM6B reversed the promoting effect on autophagy and proliferation induced by overexpression of USP7. Taken altogether, miR-15b inhibits osteoblast differentiation and autophagy to aggravate osteoporosis by targeting USP7 to regulate KDM6B expression. |
| Keywords: | autophagy differentiation KDM6B microRNA-15b osteoporosis USP7 |