Zhou Jian, Fujiwara Toshifumi, Ye Shiqiao, Li Xiaolin, Zhao Haibo
Department of Orthopedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, P. R. China.
Center for Osteoporosis and Metabolic Bone Diseases, Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Arkansas for Medical Sciences and the Central Arkansas Veterans Healthcare System, Little Rock, Arkansas, USA.
Calcif Tissue Int. 2014 Sep;95(3):209-217. doi: 10.1007/s00223-014-9883-2. Epub 2014 Jun 17.
Genetic studies in human and mice have pinpointed an essential role of Notch signaling in osteoblast and osteoclast differentiation during skeletal development and bone remodeling. However, the factors and pathways regulating Notch activation in bone cells remain largely unknown. In this in vitro study, we have provided evidence that two of the TspanC8 subfamily members of tetraspanins, Tspan-5 and Tspan-10, are up-regulated during osteoclast differentiation and knockdown of their expression by shRNAs dramatically inhibits osteoclastogenesis. Loss of Tspan-5 and Tspan-10 in osteoclast lineage cells results in attenuation of ADAM10 maturation and Notch activation. Therefore, these two tetraspanins play a critical role in osteoclast formation, at least in part, by modulating Notch signaling pathway.
人类和小鼠的遗传学研究已经明确了Notch信号通路在骨骼发育和骨重塑过程中对成骨细胞和破骨细胞分化的重要作用。然而，调节骨细胞中Notch激活的因素和途径在很大程度上仍然未知。在这项体外研究中，我们提供了证据表明，四跨膜蛋白TspanC8亚家族的两个成员Tspan-5和Tspan-10在破骨细胞分化过程中上调，并且通过短发夹RNA敲低它们的表达会显著抑制破骨细胞生成。破骨细胞谱系细胞中Tspan-5和Tspan-10的缺失导致ADAM10成熟和Notch激活减弱。因此，这两种四跨膜蛋白至少部分地通过调节Notch信号通路在破骨细胞形成中发挥关键作用。
