SEARCH:   Advanced

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Fontenay-Roupie, M Articles by Bryckaert, M Search for Related Content PubMed PubMed Citation Articles by Fontenay-Roupie, M Articles by Bryckaert, M Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Increased proliferation of bone marrow-derived fibroblasts in primitive hypertrophic osteoarthropathy with severe myelofibrosis M Fontenay-Roupie, E Dupuy, E Berrou, G Tobelem and M Bryckaert Laboratoire de Physiopathologie cellulaire et moleculaire des cellules du sang et du vaisseau, Inserm U 348, Paris, France. Pachydermoperiostosis or primary hypertrophic osteoarthropathy (HOA) is a rare congenital growth disorder of connective tissue. We report a case of severe myelofibrosis in a patient with HOA. When cultured in vitro, patient bone marrow-derived fibroblasts displayed a high proliferative potential with a shortened doubling time (24 hours v 36 to 48 hours for normal fibroblasts). The role of platelet-derived growth factor (PDGF), previously implicated in the pathogenesis of secondary acquired myelofibrosis, was studied. HOA fibroblasts expressed an increased number of PDGF-BB binding sites (300,000 sites/cell v 200,000 sites/cell for normal fibroblasts) without any modification of affinity. The increased expression of PDGF-R beta appeared to result from an accelerated rate of PDGF-R beta resynthesis with normal kinetics of endocytosis. As a consequence, a several-fold increase of PDGF-R beta tyrosine kinase activity was observed. No autocrine mechanism of growth was suspected as neither spontaneous PDGF- R beta autophosphorylation nor mitogenic activity in HOA fibroblast- conditioned medium was detected. Patient serum and platelet lysate were less potent than controls in inducing [3H]thymidine incorporation into HOA fibroblasts. This was inconsistent with a paracrine mechanism of growth. In vitro, human serum or PDGF-BB were not more mitogenic for HOA than normal fibroblasts. High levels of cyclin D1, a putative oncogene, were detected in serum-deprived HOA fibroblasts. Cyclin D1 overexpression could be implicated in the accelerated growth of these cells. Our results suggest that the mechanism of fibroblastic proliferation observed in this case of myelofibrosis might differ from those reported in other acquired myeloproliferative syndromes and could be associated with an intrinsic abnormality of HOA fibroblast growth. Volume 85, Issue 11, pp. 3229-3238, 06/01/1995 Copyright © 1995 by The American Society of Hematology CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: K. Kabashima, J.-i. Sakabe, R. Yoshiki, Y. Tabata, K. Kohno, and Y. Tokura Involvement of Wnt Signaling in Dermal Fibroblasts Am. J. Pathol., February 1, 2010; 176(2): 721 - 732. [Abstract] [Full Text] [PDF]

	Copyright © 1995 by American Society of Hematology         Online ISSN: 1528-0020