title: Bruton tyrosine kinase (Btk) suppresses osteoblastic differentiation.
abstract: The Tec family of nonreceptor tyrosine kinases has been shown to play a key role in inflammation and bone destruction. Bruton tyrosine kinase (Btk) has been the most widely studied because of its critical role in B cells. Furthermore, recent evidence has demonstrated that blocking Btk signaling is effective in ameliorating lymphoma progression and experimental arthritis. The role of Btk in osteoblastic differentiation has not been well elucidated. In this study, we demonstrated the role of Btk in osteoblastic differentiation and investigated the effects of a Btk inhibitor on osteoblastic differentiation in mouse preosteoblastic MC3T3-E1 cells, primary calvarial osteoblasts, and bone marrow stromal ST2 cells. Btk expression was detected in all three cell lines. Btk inhibition stimulated mRNA expression of osteoblastic markers (alkaline phosphatase, osteocalcin, and osterix) and promoted mineralization of the extracellular matrix. In addition, Btk knockdown caused increased mRNA expression of osteoblastic markers. Furthermore, Btk inhibition suppressed the phosphorylation of mitogen-activated protein kinase (MAPK), nuclear factor kappa B (NFκB), and protein kinase Cα (PKCα). Our results indicate that Btk may regulate osteoblastic differentiation through the MAPK, NFκB, and PKCα signaling pathways.
authors.affiliation: Department of Orthopaedic Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
authors.forename: Shoichi
authors.initials: S
authors.lastname: Kaneshiro
authors.forename: Kosuke
authors.initials: K
authors.lastname: Ebina
authors.forename: Kenrin
authors.initials: K
authors.lastname: Shi
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Yoshida
authors.forename: Dai
authors.initials: D
authors.lastname: Otsuki
authors.forename: Hideki
authors.initials: H
authors.lastname: Yoshikawa
authors.forename: Chikahisa
authors.initials: C
authors.lastname: Higuchi
mesh_terms: D000077329:Agammaglobulinaemia Tyrosine Kinase; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D002478:Cells, Cultured; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010006:Osteoblasts / Q000378:metabolism* / Q000502:physiology*; D015675:Osteocalcin / Q000378:metabolism; D010766:Phosphorylation / Q000502:physiology; D051571:Protein Kinase C-alpha / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
chemical_list: D016328:NF-kappa B; D012333:RNA, Messenger; D015675:Osteocalcin; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625949:BTK protein, human; C000625951:Btk protein, mouse; C496628:PRKCA protein, human; D051571:Protein Kinase C-alpha; D020928:Mitogen-Activated Protein Kinases; D000469:Alkaline Phosphatase