title: Downregulation of Notch modulators, tetraspanin 5 and 10, inhibits osteoclastogenesis in vitro.
abstract: 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.
authors.affiliation: 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.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhou
authors.affiliation: 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.
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Fujiwara
authors.affiliation: 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.
authors.forename: Shiqiao
authors.initials: S
authors.lastname: Ye
authors.affiliation: Department of Orthopedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, P. R. China.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Haibo
authors.initials: H
authors.lastname: Zhao
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D015536:Down-Regulation; D055785:Gene Knockdown Techniques; D015151:Immunoblotting; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D010010:Osteoclasts / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D051880:Receptors, Notch / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D059470:Tetraspanins / Q000378:metabolism*; D014162:Transfection
chemical_list: D051880:Receptors, Notch; D059470:Tetraspanins; C000597601:Tspan-10 protein, mouse; C435756:Tspan5 protein, mouse