[Cellular and molecular biology of fibrous dysplasia].
Several recent studies reflect major progress on the molecular biology and on the mechanisms of the lesions of fibrous dysplasia (monostotic and polyostotic forms) as well as the McCune-Albright syndrome. This review includes a detailed histological description of fibrous dysplasia: disorganized collagen fibers, woven bone formation, immature cytology of the osteoblasts and preosteoblastic cells. Histological lesions are also associated with an alteration of bone proteins: such as an increase in the expression of osteonectin, decrease of osteopontin and bone sialoprotein. Cell cultures of dysplasic osteoblastic cells have shown that the bone lesions are the result of abnormalities of the proliferation and differentiation of bone forming cells with a rise in CAMP levels. Poorly differentiated cells are associated with the formation of disorganized collagen fibers and with a trouble of synthesis of bone proteins. All these findings are linked to mutations of the Gs alpha (sub-unit alpha) protein. Various activating mutations are described as well as the molecular mechanisms of different forms of fibrous dysplasia, involving specially the c-fos proto-oncogene. Therapeutic implications are quoted, specially calcitonin and bisphosphonates.
Marie
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Laboratoire de biologie et pathologie de l'ostéoblaste, INSERM Unité 349 affiliée CNRS, Hôpital Lariboisière, 2, rue Ambroise-Paré, 75475 Paris. pierre.marie@insern.Irb.ap-hop-paris.fr
D002454:Cell Differentiation; D002455:Cell Division; D003094:Collagen / Q000032:analysis; D005357:Fibrous Dysplasia of Bone / Q000235:genetics* / Q000473:pathology* / Q000628:therapy; D020962:Heterotrimeric GTP-Binding Proteins / Q000235:genetics; D006801:Humans; D058574:Integrin-Binding Sialoprotein; D009154:Mutation; D010006:Osteoblasts / Q000473:pathology; D015676:Osteonectin / Q000032:analysis; D053495:Osteopontin; D000090063:Proto-Oncogene Mas; D012795:Sialoglycoproteins / Q000032:analysis
C546871:IBSP protein, human; D058574:Integrin-Binding Sialoprotein; C000715470:MAS1 protein, human; D015676:Osteonectin; D000090063:Proto-Oncogene Mas; C506895:SPP1 protein, human; D012795:Sialoglycoproteins; D053495:Osteopontin; D003094:Collagen; D020962:Heterotrimeric GTP-Binding Proteins