caa a22 4500 60546345X CHVBK 20210128100253.0 cr unu---uuuuu 210128e20150901xx s 000 0 eng 10.1007/s00774-014-0612-8 doi (NATIONALLICENCE)springer-10.1007/s00774-014-0612-8 Bruton tyrosine kinase (Btk) suppresses osteoblastic differentiation [Elektronische Daten] [Shoichi Kaneshiro, Kosuke Ebina, Kenrin Shi, Kiyoshi Yoshida, Dai Otsuki, Hideki Yoshikawa, Chikahisa Higuchi] 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. The Japanese Society for Bone and Mineral Research and Springer Japan, 2014 Bruton tyrosine kinase (Btk) nationallicence Osteoblastic differentiation nationallicence MAPK nationallicence NFκB nationallicence PKCα nationallicence Kaneshiro Shoichi Department of Orthopaedic Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, 565-0871, Suita, Osaka, Japan aut Ebina Kosuke Department of Orthopaedic Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, 565-0871, Suita, Osaka, Japan aut Shi Kenrin Department of Orthopaedic Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, 565-0871, Suita, Osaka, Japan aut Yoshida Kiyoshi Department of Orthopaedic Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, 565-0871, Suita, Osaka, Japan aut Otsuki Dai Department of Orthopaedic Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, 565-0871, Suita, Osaka, Japan aut Yoshikawa Hideki Department of Orthopaedic Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, 565-0871, Suita, Osaka, Japan aut Higuchi Chikahisa Department of Orthopaedic Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, 565-0871, Suita, Osaka, Japan aut Journal of Bone and Mineral Metabolism Springer Japan 33/5(2015-09-01), 486-495 0914-8779 33:5<486 2015 33 774 https://doi.org/10.1007/s00774-014-0612-8 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00774-014-0612-8 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Kaneshiro Shoichi Department of Orthopaedic Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, 565-0871, Suita, Osaka, Japan aut NATIONALLICENCE 700 1- Ebina Kosuke Department of Orthopaedic Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, 565-0871, Suita, Osaka, Japan aut NATIONALLICENCE 700 1- Shi Kenrin Department of Orthopaedic Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, 565-0871, Suita, Osaka, Japan aut NATIONALLICENCE 700 1- Yoshida Kiyoshi Department of Orthopaedic Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, 565-0871, Suita, Osaka, Japan aut NATIONALLICENCE 700 1- Otsuki Dai Department of Orthopaedic Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, 565-0871, Suita, Osaka, Japan aut NATIONALLICENCE 700 1- Yoshikawa Hideki Department of Orthopaedic Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, 565-0871, Suita, Osaka, Japan aut NATIONALLICENCE 700 1- Higuchi Chikahisa Department of Orthopaedic Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, 565-0871, Suita, Osaka, Japan aut NATIONALLICENCE 773 0- Journal of Bone and Mineral Metabolism Springer Japan 33/5(2015-09-01), 486-495 0914-8779 33:5<486 2015 33 774