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 cha...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.展开更多
基金supported by the National Natural Science Foundation of China (Grant numbers 11932014 and 31971239)the Sichuan Science and Technology Program (Grant numbers 2022NSFSC0765 and 2022ZYD0079)。
文摘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.
