Browsing by Subject "Bone formation"

Now showing 1 - 2 of 2
  • Thumbnail Image
    Publication
    Open Access
    Cellular and molecular alterations of osteoblasts in human disorders of bone formation
    (Murcia : F. Hernández, 1999) Marie, P.J.
    Osteogenesis is a complex process characterized sequentially by the committment of precursor cells, the proliferation of osteoprogenitor cells, the differentiation of pre-osteoblasts into mature osteoblasts and the apposition of a calcified bone matrix. Recent advances in cell and molecular biology have improved our knowledge of the cellular and molecular mechanisms controlling the different steps of bone formation in humans. Using ex vivolin vitro studies of disorders of bone formation, we showed that the recruitment of osteoprogenitor cells is the most important step controlling the rate of bone formation in both rodents and humans. Accordingly, treatments stimulating osteoblast recruitment were found to increase bone formation in experimental models of osteopenic disorders. Using models of human osteoblastic cells, we identified the profile of phenotypic markers expressed during osteoblast differentiation, and found that hormones and growth factors control osteoblastic cell proliferation and differentiation in a sequential and coordinate manner during osteogenesis in vitro. Our recent evaluation of the phenotypic osteoblast abnormalities induced by genetic mutations in the G,a and FGFR-2 genes led to the characterization of the role of these genes in the alterations of osteoblast proliferation and differentiation in humans. These studies at the histological, cellular and molecular levels provided new insight into the mechanisms that are involved in pathological bone formation in humans. It is expected that further determination of the pathogenic pathways in metabolic and genetic abnormalities in human osteoblasts will help to identify novel target genes and to conceive new therapeutic tools to stimulate bone formation in osteopenic disorders.
  • Thumbnail Image
    Publication
    Open Access
    Cellular and molecular basis of fibrous dysplasia
    (Murcia : F. Hernández, 2001) Marie, P.J.
    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 dysplastic bone lesions. The histological analysis of dysplastic 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 dysplastic bone lesions revealed that the abnormal deposition of immature bone matrix in fibrous dysplasia results from decreased differentiation and increased proliferation of osteoblastic cells. Finally, the signaling pathway involved in these osteoblastic abnormalities has been identified. It is now apparent that the constitutive elevation in cAMP leve1 induced by the Gsa mutations leads to alterations in the expression of several target genes whose promoters contain cAMP-responsive elements, such as c-fos, c-jun, 11-6 and 11-11. 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.