导读：东京医科齿科大学教授高柳广率领的研究小组18日在英国《自然》杂志网络版上报告说，他们在动物实验中发现一种蛋白质既可增加成骨细胞也可减少破骨细胞，从而保护骨骼健康。
据称，这是世界上首次发现同时作用于成骨细胞和破骨细胞的蛋白质，可能有助于开发治疗骨质疏松症、风湿性关节炎、骨折等的新方法。
研究小组分析了实验鼠成骨细胞分泌的蛋白质，发现其中与神经细胞生长等有关的蛋白质“Sema3A”不仅能够促进骨骼形成，同时还能阻碍破骨细胞的形成，遏制骨骼破坏。
研究小组通过基因操作，使一些实验鼠的“Sema3A”蛋白质不能正常发挥作用，结果与正常的实验鼠相比，前者的破骨细胞增加了约1倍，骨密度降至原有水平的三分之一以下。如果通过静脉向正常实验鼠注射这种蛋白质，它们的骨密度则出现增加。通过这种蛋白质治疗，患有骨质疏松症的实验鼠的症状得到改善。
研究小组发现，人体内也存在这种蛋白质。高柳广指出，这一发现有助于开发出在减少骨骼破坏的同时促进骨骼形成的新疗法。
Osteoprotection by semaphorin 3A
Mikihito Hayashi, Tomoki Nakashima, Masahiko Taniguchi, Tatsuhiko Kodama, Atsushi Kumanogoh & Hiroshi Takayanagi
The bony skeleton is maintained by local factors that regulate bone-forming osteoblasts and bone-resorbing osteoclasts, in addition to hormonal activity. Osteoprotegerin protects bone by inhibiting osteoclastic bone resorption, but no factor has yet been identified as a local determinant of bone mass that regulates both osteoclasts and osteoblasts. Here we show that semaphorin 3A (Sema3A) exerts an osteoprotective effect by both suppressing osteoclastic bone resorption and increasing osteoblastic bone formation. The binding of Sema3A to neuropilin-1 (Nrp1) inhibited receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation by inhibiting the immunoreceptor tyrosine-based activation motif (ITAM) and RhoA signalling pathways. In addition, Sema3A and Nrp1 binding stimulated osteoblast and inhibited adipocyte differentiation through the canonical Wnt/β-catenin signalling pathway. The osteopenic phenotype in Sema3a−/− mice was recapitulated by mice in which the Sema3A-binding site of Nrp1 had been genetically disrupted. Intravenous Sema3A administration in mice increased bone volume and expedited bone regeneration. Thus, Sema3A is a promising new therapeutic agent in bone and joint diseases.
文献链接：https://www.nature.com/nature/journal/vaop/ncurrent/full/nature11000.html
