Regulation of human cranial osteoblast phenotype by FGF-2, FGFR-2 and BMP-2 signaling P.J. Marie, F. Debiais and E. Haÿ INSERM U349, Hopital Lariboisière, Paris, France Offprint requests to: Pierre. J. Marie, Laboratory of Osteoblast Biology and Pathology, INSERM Unité 349 affiliated CNRS, Hopital Lariboisière, 2 rue Ambroise Paré, 75475 Paris Cedex 10, France. Fax: 33 1 49 95 84 52. e-mail: pierre.marie@inserm.lrb.ap-hop-paris.fr
Summary. The formation of cranial bone requires the
differentiation of osteoblasts from undifferentiated mesenchymal
cells. The balance between osteoblast recruitment, proliferation,
differentiation and apoptosis in sutures between cranial bones
is essential for calvarial bone formation. The mechanisms that
control human osteoblasts during normal calvarial bone formation
and premature suture ossification (craniosynostosis) begin to
be understood. Our studies of the human calvaria osteoblast phenotype
and calvarial bone formation showed that premature fusion of the
sutures in non-syndromic and syndromic (Apert syndrome) craniosynostoses
results from precocious osteoblast differentiation. We showed
that Fibroblast Growth Factor-2 (FGF-2), FGF receptor-2 (FGFR-2)
and Bone Morphogenetic Protein-2 (BMP-2), three essential factors
involved in skeletal development, regulate the proliferation,
differentiation and apoptosis in human calvaria osteoblasts. Mechanisms
that induce the differentiated osteoblast phenotype have also
been identified in human calvaria osteoblasts. We demonstrated
the implication of molecules (N-cadherin, Il-1) and signaling
pathways (src, PKC) by which these local factors modulate human
calvaria osteoblast differentiation and apoptosis. The identification
of these essential signaling molecules provides new insights into
the pathways controlling the differentiated osteoblast phenotype,
and leads to a more comprehensive view in the mechanisms that
control normal and premature cranial ossification in humans. Histol.
Histopathol. 17, 877-885 (2002) |