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The role of c-Src kinase in the regulation of osteoclast function

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Modern Rheumatology

Abstract

The targeted disruption of c-Src impairs osteoclast bone resorbing activity, causing osteopetrosis. Although it has been reported that restoring only the c-Src adaptor function at least partly rescues the skeletal phenotypes, the importance of c-Src kinase activity remains controversial. We here highlight the contributions of the Src adaptor and kinase activities in cytoskeletal organization and osteoclast function using adenovirus vectors containing various mutants of Src or Pyk2. In addition, we describe the importance of c-Src in mitochondria, where it phosphorylates cytochrome c oxidase (Cox). Src-induced Cox activity is also required for bone resorbing activity of osteoclasts that require high levels of ATP. Thus, c-Src kinase activity not only on the plasma membrane but also within mitochondria is essential for the regulation of osteoclastic bone resorption.

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Authors and Affiliations

  1. Department of Orthopaedic Surgery, Tokyo Metropolitan Komagome Hospital, 3-18-22 Komagome, Bunkyo-ku, Tokyo, 113-8677, Japan

    Tsuyoshi Miyazaki

  2. Department of Orthopaedic Surgery, Faculty of Medicine, The University of Tokyo, Tokyo, Japan

    Sakae Tanaka

  3. Department of Cell Biology and Orthopaedics, Yale University School of Medicine, New Haven, CT, USA

    Archana Sanjay & Roland Baron

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  1. Tsuyoshi Miyazaki
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  2. Sakae Tanaka
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  4. Roland Baron
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Correspondence to Tsuyoshi Miyazaki.

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Miyazaki, T., Tanaka, S., Sanjay, A. et al. The role of c-Src kinase in the regulation of osteoclast function. Mod Rheumatol 16, 68–74 (2006). https://doi.org/10.1007/s10165-006-0460-z

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