Publication: Cellular and molecular basis of fibrous dysplasia
Authors
Marie, P.J.
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Publisher
Murcia : F. Hernández
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DOI
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info:eu-repo/semantics/article
Description
Abstract
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.
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