Division of Hard Tissue Research, Institute for Oral Science, Matsumoto Dental University, 1780 Gobara, Hiro-oka, Shiojiri, Nagano, 399-0781, Japan.
J Bone Miner Metab. 2019 Jan;37(1):9-17. doi: 10.1007/s00774-018-0971-7. Epub 2018 Oct 24.
Osteocytes are embedded in bone matrices and are connected to each other to respond to mechanical loading on bone. Recent studies have demonstrated the roles of mechanical loading in bone accrual. Bone responds to mechanical loading by decreasing the expression of sclerostin, an inhibitor of Wnt/β-catenin signals, in osteocytes. This increases bone mass because the activation of Wnt/β-catenin signals in bone microenvironments promotes bone formation and suppresses bone resorption. Thus, in recent years, sclerostin have attracted increasing attention in bone metabolism. However, the regulatory mechanism of sclerostin expression during bone remodeling has not been fully elucidated. In this review, we summarized the regulation of bone formation and resorption by Wnt signals, a Wnt/β-catenin signal inhibitor sclerostin, and molecular mechanisms by which the expression of sclerostin is suppressed by mechanical loading and parathyroid hormone. We also discuss a possibility that osteoclasts suppress the expression of sclerostin during bone remodeling, which in turn, promote bone formation. The effectiveness of an anti-sclerostin antibody with anti-dickkopf-1 antibody for increasing bone mass was discussed.
成骨细胞嵌入在骨基质中，并彼此相连，以响应骨骼上的机械负荷。最近的研究表明机械负荷在骨量增加中的作用。骨骼通过降低成骨细胞中骨硬化蛋白（Wnt/β-catenin 信号的抑制剂）的表达来响应机械负荷。这增加了骨量，因为骨微环境中 Wnt/β-catenin 信号的激活促进了骨形成并抑制了骨吸收。因此，近年来，骨硬化蛋白在骨代谢中受到越来越多的关注。然而，骨重塑过程中骨硬化蛋白表达的调节机制尚未完全阐明。在这篇综述中，我们总结了 Wnt 信号、Wnt/β-catenin 信号抑制剂骨硬化蛋白对骨形成和骨吸收的调节作用，以及机械负荷和甲状旁腺激素抑制骨硬化蛋白表达的分子机制。我们还讨论了破骨细胞在骨重塑过程中抑制骨硬化蛋白表达的可能性，这反过来又促进了骨形成。讨论了抗骨硬化蛋白抗体与抗 Dickkopf-1 抗体联合使用增加骨量的有效性。
