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Original Article | Open Access

Annexin A5 derived from matrix vesicles protects against osteoporotic bone loss via mineralization

Guanyue Su1,Demao Zhang1,Tiantian Li1Tong Pei1Jie Yang1Shasha Tu1Sijun Liu1Jie Ren1Yaojia Zhang1Mengmeng Duan2Xinrui Yang1Yang Shen1Chenchen Zhou2Jing Xie2 ( )Xiaoheng Liu1( )
Institute of Biomedical Engineering, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu 610041, China
State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China

These authors contributed equally: Guanyue Su, Demao Zhang

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Abstract

Matrix vesicles (MVs) have shown strong effects in diseases such as vascular ectopic calcification and pathological calcified osteoarthritis and in wound repair of the skeletal system due to their membranous vesicle characteristics and abundant calcium and phosphorus content. However, the role of MVs in the progression of osteoporosis is poorly understood. Here, we report that annexin A5, an important component of the matrix vesicle membrane, plays a vital role in bone matrix homeostasis in the deterioration of osteoporosis. We first identified annexin A5 from adherent MVs but not dissociative MVs of osteoblasts and found that it could be sharply decreased in the bone matrix during the occurrence of osteoporosis based on ovariectomized mice. We then confirmed its potential in mediating the mineralization of the precursor osteoblast lineage via its initial binding with collagen type Ⅰ to achieve MV adhesion and the subsequent activation of cellular autophagy. Finally, we proved its protective role in resisting bone loss by applying it to osteoporotic mice. Taken together, these data revealed the importance of annexin A5, originating from adherent MVs of osteoblasts, in bone matrix remodeling of osteoporosis and provided a new strategy for the treatment and intervention of bone loss.

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Bone Research
Article number: 60
Cite this article:
Su G, Zhang D, Li T, et al. Annexin A5 derived from matrix vesicles protects against osteoporotic bone loss via mineralization. Bone Research, 2023, 11: 60. https://doi.org/10.1038/s41413-023-00290-9

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Received: 24 April 2023
Revised: 23 July 2023
Accepted: 31 August 2023
Published: 09 November 2023
© The Author(s) 2023

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