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Interleukin-1 receptor-associated kinase-4 (IRAK4) promotes inflammatory osteolysis by activating osteoclasts and inhibiting formation of foreign body giant cells.
Katsuyama, Eri; Miyamoto, Hiroya; Kobayashi, Tami; Sato, Yuiko; Hao, Wu; Kanagawa, Hiroya; Fujie, Atsuhiro; Tando, Toshimi; Watanabe, Ryuichi; Morita, Mayu; Miyamoto, Kana; Niki, Yasuo; Morioka, Hideo; Matsumoto, Morio; Toyama, Yoshiaki; Miyamoto, Takeshi.
Afiliación
  • Katsuyama E; From the Departments of Orthopedic Surgery.
  • Miyamoto H; From the Departments of Orthopedic Surgery.
  • Kobayashi T; From the Departments of Orthopedic Surgery, Integrated Bone Metabolism and Immunology.
  • Sato Y; From the Departments of Orthopedic Surgery, Musculoskeletal Reconstruction and Regeneration Surgery, and.
  • Hao W; From the Departments of Orthopedic Surgery.
  • Kanagawa H; From the Departments of Orthopedic Surgery.
  • Fujie A; From the Departments of Orthopedic Surgery.
  • Tando T; From the Departments of Orthopedic Surgery.
  • Watanabe R; From the Departments of Orthopedic Surgery.
  • Morita M; Dentistry and Oral Surgery, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo 160-8582, Japan.
  • Miyamoto K; From the Departments of Orthopedic Surgery.
  • Niki Y; From the Departments of Orthopedic Surgery.
  • Morioka H; From the Departments of Orthopedic Surgery.
  • Matsumoto M; From the Departments of Orthopedic Surgery.
  • Toyama Y; From the Departments of Orthopedic Surgery.
  • Miyamoto T; From the Departments of Orthopedic Surgery, Integrated Bone Metabolism and Immunology, miyamoto@z5.keio.jp.
J Biol Chem ; 290(2): 716-26, 2015 Jan 09.
Article en En | MEDLINE | ID: mdl-25404736
Formation of foreign body giant cells (FBGCs) occurs following implantation of medical devices such as artificial joints and is implicated in implant failure associated with inflammation or microbial infection. Two major macrophage subpopulations, M1 and M2, play different roles in inflammation and wound healing, respectively. Therefore, M1/M2 polarization is crucial for the development of various inflammation-related diseases. Here, we show that FBGCs do not resorb bone but rather express M2 macrophage-like wound healing and inflammation-terminating molecules in vitro. We also found that FBGC formation was significantly inhibited by inflammatory cytokines or infection mimetics in vitro. Interleukin-1 receptor-associated kinase-4 (IRAK4) deficiency did not alter osteoclast formation in vitro, and IRAK4-deficient mice showed normal bone mineral density in vivo. However, IRAK4-deficient mice were protected from excessive osteoclastogenesis induced by IL-1ß in vitro or by LPS, an infection mimetic of Gram-negative bacteria, in vivo. Furthermore, IRAK4 deficiency restored FBGC formation and expression of M2 macrophage markers inhibited by inflammatory cytokines in vitro or by LPS in vivo. Our results demonstrate that osteoclasts and FBGCs are reciprocally regulated and identify IRAK4 as a potential therapeutic target to inhibit stimulated osteoclastogenesis and rescue inhibited FBGC formation under inflammatory and infectious conditions without altering physiological bone resorption.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Células Gigantes de Cuerpo Extraño / Diferenciación Celular / Quinasas Asociadas a Receptores de Interleucina-1 / Inflamación Tipo de estudio: Risk_factors_studies Límite: Animals Idioma: En Revista: J Biol Chem Año: 2015 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Células Gigantes de Cuerpo Extraño / Diferenciación Celular / Quinasas Asociadas a Receptores de Interleucina-1 / Inflamación Tipo de estudio: Risk_factors_studies Límite: Animals Idioma: En Revista: J Biol Chem Año: 2015 Tipo del documento: Article Pais de publicación: Estados Unidos