RESUMO
We investigated whether transforming growth factor-beta (TGF-beta) stimulates the induction of heat shock protein (HSP) 27 and HSP70 in osteoblast-like MC3T3-E1 cells and the mechanism underlying the induction. TGF-beta increased the level of HSP27 but had no effect on the HSP70 level. TGF-beta stimulated the accumulation of HSP27 dose-dependently, and induced an increase in the level of mRNA for HSP27. TGF-beta induced the phosphorylation of p44/p42 mitogen-activated protein (MAP) kinase and p38 MAP kinase. The HSP27 accumulation induced by TGF-beta was significantly suppressed by PD98059, an inhibitor of the upstream kinase of p44/p42 MAP kinase, or SB203580, an inhibitor of p38 MAP kinase. PD98059 and SB203580 suppressed the TGF-beta-stimulated increase in the level of mRNA for HSP27. Retinoic acid, a vitamin A (retinol) metabolite, which alone had little effect on the HSP27 level, markedly enhanced the HSP27 accumulation stimulated by TGF-beta. Retinoic acid enhanced the TGF-beta-induced increase of mRNA for HSP27. The amplification of TGF-beta-stimulated HSP27 accumulation by retinoic acid was reduced by PD98059 or SB203580. Retinoic acid failed to affect the TGF-beta-induced phosphorylation of p44/p42 MAP kinase or p38 MAP kinase. These results strongly suggest that p44/p42 MAP kinase and p38 MAP kinase take part in the pathways of the TGF-beta-stimulated HSP27 induction in osteoblasts, and that retinoic acid upregulates the TGF-beta-stimulated HSP27 induction at a point downstream from p44/p42 MAP kinase and p38 MAP kinase.
Assuntos
Proteínas de Choque Térmico/biossíntese , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Osteoblastos/efeitos dos fármacos , Tretinoína/farmacologia , Animais , Northern Blotting , Linhagem Celular , Ativação Enzimática , Flavonoides/farmacologia , Proteínas de Choque Térmico/genética , Imidazóis/farmacologia , Camundongos , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno , Osteoblastos/metabolismo , Fosforilação/efeitos dos fármacos , Piridinas/farmacologia , RNA Mensageiro/análise , Transdução de Sinais , Fator de Crescimento Transformador beta/farmacologia , Regulação para Cima , Proteínas Quinases p38 Ativadas por MitógenoRESUMO
We report a case of atlantoaxial vertical subluxation with mandibular micrognathia associated with juvenile rheumatoid arthritis. The patient was treated by odontoidectomy via the transoral approach and required a sagittal split mandibular osteotomy because of the mandibular micrognathia. The clinical outcome was excellent.