Resumen de Cellular and molecular basis of fibrous dysplasia
Recent advances have been made in the cellular and molecular mechanisms involved in monostotic and polyostotic fibrous dysplasia, a rare nonmalignant disease causing bone deformations and fractures. The molecular basis of fibrous dysplasia has been clarified when mutations affecting the stimulatory a subunit of G protein (Gs) have been found in dyspla tic bone lesions. The histological analysis of dyspla tic lesions revealed that the mutations in Gsa caused abnormalities in cells of the osteoblastic lineage and therefore in the bone matrix. Further in vitro analyses of bone cells from mutant dysp lastic bone lesions revealed that the abnormal deposition of immature bone matrix in fibrous dysplasia results from decrea ed differentiation and increased proliferation of osteoblastic cells. Finally, the ignaling pathway involved in these osteoblastic abnormalitie has been identified. It i now apparent that the constitutive elevation in cAMP level induced by the Gsa mutations leads to alterations in the expression of several target genes whose promoters contain cAMP-respon ive elements, uch as c-fos, c-jun, Il-6 and I1-11. This in turn affects the transcription and expression of downstream genes and results in the alterations of osteoblast recruitment and function in dysplastic bone lesions.
These mechanisms provide a cellular and molecular basis for the alterations in bone cells and bone matrix in fibrous dysplasia.
