Division of Endocrinology and Metabolism, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea.
BMB Rep. 2018 Jun;51(6):263-264. doi: 10.5483/bmbrep.2018.51.6.109.
We identified osteoclast-derived SLIT3 as a new coupling factor using fractionated secretomics. Coupling links bone resorption to bone formation. SLIT3 stimulated the recruitment and proliferation of osteoblasts into bone remodeling sites via activation of β-catenin. Autocrine signaling by SLIT3 also inhibited bone resorption by suppressing the fusion and differentiation of pre-osteoclasts. All mice lacking Slit3 or its receptor Robo1 showed an osteopenic phenotype with low bone formation and high bone resorption. A small truncated recombinant SLIT3 protein increased bone mass in an osteopenic mouse model. These results suggest that SLIT3 is a novel therapeutic target in metabolic bone diseases. [BMB Reports 2018; 51(6): 263-264].
我们通过分馏的分泌组学鉴定破骨细胞衍生的 SLIT3 作为一种新的偶联因子。偶联将骨吸收与骨形成联系起来。SLIT3 通过激活β-连环蛋白刺激成骨细胞招募和增殖到骨重塑部位。SLIT3 的自分泌信号还通过抑制破骨前体细胞的融合和分化来抑制骨吸收。所有缺乏 Slit3 或其受体 Robo1 的小鼠均表现出骨质疏松表型，其特征是骨形成率低，骨吸收率高。一种小的截断重组 SLIT3 蛋白增加了骨质疏松小鼠模型的骨量。这些结果表明 SLIT3 是代谢性骨病的一个新的治疗靶点。[BMB 报告 2018；51(6): 263-264]。
