TY - JOUR
T1 - Downregulation of Notch modulators, tetraspanin 5 and 10, inhibits osteoclastogenesis in vitro
AU - Zhou, Jian
AU - Fujiwara, Toshifumi
AU - Ye, Shiqiao
AU - Li, Xiaolin
AU - Zhao, Haibo
N1 - Funding Information:
The authors would like to thank Drs. Stavros C Manolagas and Charles A Obrien for their critic of the manuscript prior to submission and Erin Hogan for her support in microscopic analysis. This work was supported by National Institutes of Health Grants AR062012 and P01 AG13918. This work was also supported by the University of Arkansas for Medical Sciences Tobacco Settlement Funds provided by the Arkansas Biosciences Institute.
PY - 2014/9
Y1 - 2014/9
N2 - 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.
AB - 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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U2 - 10.1007/s00223-014-9883-2
DO - 10.1007/s00223-014-9883-2
M3 - Article
C2 - 24935633
AN - SCOPUS:84906350850
SN - 0171-967X
VL - 95
SP - 209
EP - 217
JO - Calcified Tissue International
JF - Calcified Tissue International
IS - 3
ER -
