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Bruton tyrosine kinase (Btk) suppresses osteoblastic differentiation

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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.

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All authors have no conflicts of interest.

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Authors and Affiliations

  1. Department of Orthopaedic Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan

    Shoichi Kaneshiro, Kosuke Ebina, Kenrin Shi, Kiyoshi Yoshida, Dai Otsuki, Hideki Yoshikawa & Chikahisa Higuchi

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  1. Shoichi Kaneshiro
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  2. Kosuke Ebina
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  3. Kenrin Shi
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  4. Kiyoshi Yoshida
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  5. Dai Otsuki
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  6. Hideki Yoshikawa
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  7. Chikahisa Higuchi
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Correspondence to Chikahisa Higuchi.

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Kaneshiro, S., Ebina, K., Shi, K. et al. Bruton tyrosine kinase (Btk) suppresses osteoblastic differentiation. J Bone Miner Metab 33, 486–495 (2015). https://doi.org/10.1007/s00774-014-0612-8

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  • DOI: https://doi.org/10.1007/s00774-014-0612-8

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