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.

基质囊泡（MVs）由于其膜囊泡特性和丰富的钙磷含量，在血管异位钙化、病理性钙化骨关节炎等疾病以及骨骼系统伤口修复中显示出强大的作用。然而，人们对 MV 在骨质疏松症进展中的作用知之甚少。在这里，我们报道膜联蛋白A5是基质囊泡膜的重要组成部分，在骨质疏松症恶化过程中在骨基质稳态中发挥着至关重要的作用。我们首先从成骨细胞的贴壁MV而非解离MV中鉴定出膜联蛋白A5，并基于卵巢切除小鼠发现在骨质疏松发生期间其在骨基质中急剧减少。然后，我们证实了它通过与 I 型胶原蛋白的初始结合来介导前体成骨细胞谱系矿化的潜力，以实现 MV 粘附和随后的细胞自噬激活。最后，我们通过将其应用于骨质疏松小鼠，证明了其对抗骨质流失的保护作用。综上所述，这些数据揭示了源自成骨细胞贴壁MV的膜联蛋白A5在骨质疏松症骨基质重塑中的重要性，并为骨丢失的治疗和干预提供了新策略。