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Silencing Proteasome 26S Subunit ATPase 2 (PSMC2) Protects the Osteogenic Differentiation In Vitro and Osteogenesis In Vivo

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Abstract

Osteoporosis is a commonly seen degenerative bone disorder in the elderly and postmenopausal women, with a low bone mineral density as a major risk factor. The osteogenic potential of bone marrow stromal cells (BMSCs) showed to be impaired during osteoporosis. We established a postmenopausal osteoporosis model in ovariectomized (OVX) mice and found the upregulation of proteasome 26S subunit ATPase 2 (PSMC2) in OVX mice. PSMC2 silencing improved OVX-impaired biomechanical properties of mice femur, OVX-decreased BMD, and OVX-destroyed bone structure. Histopathological analysis indicated that PSMC2 silencing improved bone trabecular structure and increased the contents of collagen fibers and newly formed bone or cartilage in OVX mice. In the meantime, PSMC2 silencing increased Runx2, PI3K, Wnt3a, and β-catenin protein contents while reduced CTSK protein. Within BMSCs isolated from OVX mice, PSMC2 silencing promoted BMSC osteogenic differentiation and elevated osteogenic markers’ protein contents, including HOXA10, Runx2, OCN, OPN, and COL1A2. In conclusion, PSMC2 expression is upregulated in the postmenopausal osteoporosis model in OVX mice. PSMC2 silencing promotes the osteogenic differentiation of BMSCs in vitro, promotes bone formation, and inhibits bone resorption in vivo.

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Funding

This study was supported by Innovative Research and Development project of Hunan Development and Reform Commission (2019412).

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Author notes

  1. Bin Zhou, and Kun Peng contribute equally to this study.

Authors and Affiliations

  1. Department of Spine Surgery, The Second Xiangya Hospital, Central South University, Changsha, 410011, China

    Bin Zhou, Kun Peng, Guoqiang Wang, Weihua Chen & Yijun Kang

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  1. Bin Zhou
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  2. Kun Peng
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  5. Yijun Kang
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Contributions

Bin Zhou performed the experiments and wrote the paper. Kun Peng and Weihua Chen coordinated the study. Guoqiang Wang collected the samples and assisted with the experiments. Yijun Kang conceived the study, designed the experiments, and revised the paper. All the authors have read and approved the final manuscript.

Corresponding author

Correspondence to Yijun Kang.

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Disclosure

Bin Zhou, Kun Peng, Guoqiang Wang, Weihua Chen, and Yijun Kang declared that they have no conflict of interest.

Human and Animal Rights and Informed Consent

All experiments were carried out according to the Guide for the Care and Use of Laboratory Animals (National Institutes of Health, Bethesda, MD, USA) and were approved by the Ethics Committee of the Second Xiangya Hospital, Central South University. There are no human sujects in the present study.

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Zhou, B., Peng, K., Wang, G. et al. Silencing Proteasome 26S Subunit ATPase 2 (PSMC2) Protects the Osteogenic Differentiation In Vitro and Osteogenesis In Vivo. Calcif Tissue Int 109, 44–54 (2021). https://doi.org/10.1007/s00223-021-00819-2

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