Journal
CALCIFIED TISSUE INTERNATIONAL
Volume 95, Issue 3, Pages 209-217Publisher
SPRINGER
DOI: 10.1007/s00223-014-9883-2
Keywords
Tetraspanin; ADAM10; Notch; Osteoclast; Bone resorption
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Funding
- National Institutes of Health [AR062012, P01 AG13918]
- University of Arkansas for Medical Sciences Tobacco Settlement Funds by the Arkansas Biosciences Institute
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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.
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