title: Role of FK506 binding protein 5 (FKBP5) in osteoclast differentiation.
abstract: OBJECTIVE
  We previously disclosed the enhanced expression of FK506 binding protein 5 (FKBP5) messenger RNA (mRNA) in bone marrow (BM) CD34(+) cells in rheumatoid arthritis (RA), in which systemic osteoporosis takes place. Since BM CD34(+) cells are precursors of osteoclasts, it is possible that FKBP5 overexpression might lead to osteoporosis by affecting osteoclastogenesis. We therefore explore the influences of FKBP5 in osteoclast differentiation.
  
  
  METHODS
  Stable transfectants of RAW264.7 overexpressing murine FKBP5 gene were established. Osteoclast differentiation was induced by receptor activator of nuclear factor kappa B (NF-κB) ligand and was evaluated by tartrate-resistant acid phosphatase (TRAP) staining and pit formation assay.
  
  
  RESULTS
  FKBP5 transfectants of RAW264.7 generated higher numbers of TRAP-positive multinucleated cells with increased activity of pit formation on calcium phosphate-coated culture slides than mock transfectants. The enhancement of osteoclast differentiation of FKBP5 transfectants was only partially inhibited by N-acetyl L-cysteine. Finally, glucocorticoid enhanced FKBP5 mRNA expression as well as osteoclast differentiation of RAW264.7 cells in a dose-dependent manner.
  
  
  CONCLUSIONS
  These results indicate that FKBP5 promotes osteoclast differentiation by a mechanism distinct from NF-κB activation. Moreover, the data suggest that FKBP5 might play a role in bone destruction and development of osteoporosis in RA as well as in glucocorticoid-induced osteoporosis.
authors.affiliation: Department of Rheumatology and Infectious Diseases, Kitasato University School of Medicine, 1-15-1 Kitasato, Sagamihara, Kanagawa, 228-8555, Japan.
authors.forename: Miho
authors.initials: M
authors.lastname: Kimura
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Nagai
authors.forename: Reiko
authors.initials: R
authors.lastname: Matsushita
authors.forename: Atsushi
authors.initials: A
authors.lastname: Hashimoto
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Miyashita
authors.forename: Shunsei
authors.initials: S
authors.lastname: Hirohata
mesh_terms: D000818:Animals; D001172:Arthritis, Rheumatoid / Q000378:metabolism; D001862:Bone Resorption / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D002478:Cells, Cultured; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D010024:Osteoporosis / Q000378:metabolism; D022021:Tacrolimus Binding Proteins / Q000235:genetics / Q000378:metabolism*; D000099159:Tacrolimus Binding Protein 5
chemical_list: D016328:NF-kappa B; D022021:Tacrolimus Binding Proteins; D000099159:Tacrolimus Binding Protein 5