School of Pharmaceutical Sciences, Shoolini University, Solan, Himachal Pradesh, 173212, India.
Curr Drug Targets. 2021;22(1):77-104. doi: 10.2174/1389450121666200910160404.
Bone is one of the dynamic tissues in the human body that undergoes continuous remodelling through subsequent actions of bone cells, osteoclasts, and osteoblasts. Several signal transduction pathways are involved in the transition of mesenchymal stem cells into osteoblasts. These primarily include Runx2, ATF4, Wnt signaling and sympathetic signalling. The differentiation of osteoclasts is controlled by M-CSF, RANKL, and costimulatory signalling. It is well known that bone remodelling is regulated through receptor activator of nuclear factor-kappa B ligand followed by binding to RANK, which eventually induces the differentiation of osteoclasts. The resorbing osteoclasts secrete TRAP, cathepsin K, MMP-9 and gelatinase to digest the proteinaceous matrix of type I collagen and form a saucer-shaped lacuna along with resorption tunnels in the trabecular bone. Osteoblasts secrete a soluble decoy receptor, osteoprotegerin that prevents the binding of RANK/RANKL and thus moderating osteoclastogenesis. Moreover, bone homeostasis is also regulated by several growth factors like, cytokines, calciotropic hormones, parathyroid hormone and sex steroids. The current review presents a correlation of the probable molecular targets underlying the regulation of bone mass and the role of essential metabolic elements in bone remodelling. Targeting these signaling pathways may help to design newer therapies for treating bone diseases.
骨骼是人体中一种具有活力的组织，通过成骨细胞、破骨细胞和间充质干细胞的后续作用不断进行重塑。几种信号转导通路参与了间充质干细胞向成骨细胞的转化。这些通路主要包括 Runx2、ATF4、Wnt 信号和交感神经信号。破骨细胞的分化受 M-CSF、RANKL 和共刺激信号的控制。众所周知，核因子-κB 配体受体激活剂通过与 RANK 结合来调节骨重塑，从而最终诱导破骨细胞的分化。破骨细胞分泌 TRAP、组织蛋白酶 K、MMP-9 和明胶酶来消化 I 型胶原的蛋白基质，并在小梁骨中形成碟形陷窝和吸收隧道。成骨细胞分泌可溶性诱饵受体骨保护素，防止 RANK/RANKL 的结合，从而调节破骨细胞的生成。此外，骨稳态还受多种生长因子（如细胞因子、钙调节激素、甲状旁腺激素和性激素）的调节。本综述介绍了调节骨量的潜在分子靶点以及骨代谢中必需代谢元素的作用之间的相关性。针对这些信号通路可能有助于设计治疗骨骼疾病的新疗法。
