Troen Bruce R
Geriatric Research Education and Clinical Center, Miami Veterans Administration Medical Center, Miami, FL 33125, USA.
Exp Gerontol. 2003 Jun;38(6):605-14. doi: 10.1016/s0531-5565(03)00069-x.
Osteoporosis is one of the leading causes of morbidity in the elderly and is characterized by a progressive loss of total bone mass and bone density. Bone loss in osteoporosis is due to the persistent excess of osteoclastic bone resorption over osteoblastic bone formation. Receptor activator of NFkappaB ligand (RANKL) critically regulates both osteoclast differentiation and activation. TRAFs appear to be central coupling molecules in the signal transduction pathways that regulate osteoclastogenesis, cathepsin K is the major mediator of osteoclastic bone resorption, and sex steroids and aging also affect osteoclastogenesis and osteoclast activity. However, bone homeostasis depends upon the intimate coupling of bone formation and bone resorption, wherein both osteoclasts and osteoblasts exert vital stimulatory and inhibitory effects upon each other via molecules such as RANKL, TGFbeta, PDGF, BMP2, and Mim-1. This review will highlight some of the major features of the complex circuit of cytokines, growth factors, and hormones that underlies the formation and function of osteoclasts and the dynamic equilibrium that marks the interaction between osteoclasts and osteoblasts.
骨质疏松症是老年人发病的主要原因之一，其特征是骨总量和骨密度逐渐丧失。骨质疏松症中的骨质流失是由于破骨细胞骨吸收持续超过成骨细胞骨形成。核因子κB受体活化因子配体（RANKL）对破骨细胞的分化和活化起着关键调节作用。肿瘤坏死因子受体相关因子似乎是调节破骨细胞生成信号转导途径中的核心偶联分子，组织蛋白酶K是破骨细胞骨吸收的主要介质，性激素和衰老也会影响破骨细胞生成和破骨细胞活性。然而，骨稳态取决于骨形成和骨吸收的紧密耦合，其中破骨细胞和成骨细胞都通过RANKL、转化生长因子β、血小板衍生生长因子、骨形态发生蛋白2和Mim-1等分子对彼此发挥重要的刺激和抑制作用。本综述将重点介绍细胞因子、生长因子和激素复杂网络的一些主要特征，这些特征构成了破骨细胞形成和功能的基础，以及标志着破骨细胞和成骨细胞相互作用的动态平衡。
