A bone-protective role for IL-17 receptor signaling in ovariectomy-induced bone loss.
Eur J Immunol
; 39(10): 2831-9, 2009 Oct.
Article
en En
| MEDLINE
| ID: mdl-19731364
ABSTRACT
Post-menopausal osteoporosis is considered to be an inflammatory process, in which numerous pro-inflammatory and T-cell-derived cytokines play a bone-destructive role. IL-17A is the signature cytokine of the pro-inflammatory Th17 population and plays dichotomous roles in diseases that affect bone turnover. Although IL-17A promotes bone loss in rheumatoid arthritis, it is protective against pathogen-induced bone destruction in a periodontal disease model. We used a model of ovariectomy-induced osteoporosis (OVX) in IL-17 receptor (IL-17RA)(-/-) mice to evaluate the role of the IL-17A in bone loss caused by estrogen deficiency. Unexpectedly, IL-17RA(-/-) mice were consistently and markedly more susceptible to OVX-induced bone loss than controls. There were no changes in prototypical Th1, Th2 or Th17 cytokines in serum that could account for increased bone loss. However, IL-17RA(-/-) mice exhibited constitutively elevated leptin, which further increased following OVX. Consistently, IL-17A and IL-17F treatment of 3T3-L1 pre-adipocytes inhibited adipogenesis, leading to reduced production of leptin. In addition to its role in regulating metabolism and satiety, leptin can regulate bone turnover. Accordingly, these data show that IL-17A negatively regulates adipogenesis and subsequent leptin expression, which correlates with increased bone destruction during OVX.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Osteoporosis
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Ovariectomía
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Transducción de Señal
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Estrógenos
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Receptores de Interleucina-17
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Año:
2009
Tipo del documento:
Article