Division of Molecular Signaling and Biochemistry, Department of Health Improvement, Kyushu Dental University, Kitakyushu 803-8580, Japan.
Int J Mol Sci. 2022 May 14;23(10):5508. doi: 10.3390/ijms23105508.
Osteoclasts, which resorb the bone, and osteoblasts, which form the bone, are the key cells regulating bone homeostasis. Osteoporosis and other metabolic bone diseases occur when osteoclast-mediated bone resorption is increased and bone formation by osteoblasts is decreased. Analyses of tyrosine kinase Src-knockout mice revealed that Src is essential for bone resorption by osteoclasts and suppresses bone formation by osteoblasts. Src-knockout mice exhibit osteopetrosis. Therefore, Src is a potential target for osteoporosis therapy. However, Src is ubiquitously expressed in many tissues and is involved in various biological processes, such as cell proliferation, growth, and migration. Thus, it is challenging to develop effective osteoporosis therapies targeting Src. To solve this problem, it is necessary to understand the molecular mechanism of Src function in the bone. Src expression and catalytic activity are maintained at high levels in osteoclasts. The high activity of Src is essential for the attachment of osteoclasts to the bone matrix and to resorb the bone by regulating actin-related molecules. Src also inhibits the activity of Runx2, a master regulator of osteoblast differentiation, suppressing bone formation in osteoblasts. In this paper, we introduce the molecular mechanisms of Src in osteoclasts and osteoblasts to explore its potential for bone metabolic disease therapy.
破骨细胞负责吸收骨骼，成骨细胞则负责形成骨骼，它们是调节骨骼内稳态的关键细胞。当破骨细胞介导的骨吸收增加，而成骨细胞形成的骨骼减少时，就会发生骨质疏松症和其他代谢性骨病。对酪酸激酶Src 敲除小鼠的分析表明，Src 对于破骨细胞的骨吸收是必需的，并且抑制成骨细胞的骨形成。Src 敲除小鼠表现出骨质增生。因此，Src 是骨质疏松症治疗的潜在靶点。然而，Src 在许多组织中广泛表达，并参与各种生物过程，如细胞增殖、生长和迁移。因此，开发针对 Src 的有效骨质疏松症治疗方法具有挑战性。为了解决这个问题，有必要了解 Src 在骨骼中的功能的分子机制。Src 的表达和催化活性在破骨细胞中维持在高水平。Src 的高活性对于破骨细胞附着在骨基质上以及通过调节与肌动蛋白相关的分子来吸收骨骼是必不可少的。Src 还抑制成骨细胞分化的主调控因子 Runx2 的活性，从而抑制成骨细胞中的骨形成。在本文中，我们介绍了 Src 在破骨细胞和成骨细胞中的分子机制，以探索其在骨代谢疾病治疗中的潜力。
