Role of FK506 binding protein 5 (FKBP5) in osteoclast differentiation.
Mod Rheumatol
; 23(6): 1133-9, 2013 Nov.
Article
in En
| MEDLINE
| ID: mdl-23263277
ABSTRACT
OBJECTIVES:
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Osteoclasts
/
Cell Differentiation
/
Tacrolimus Binding Proteins
Limits:
Animals
Language:
En
Journal:
Mod Rheumatol
Year:
2013
Document type:
Article
Affiliation country: