Effect of endothelin-1 on osteoblastic differentiation is modified by the level of connexin43: comparative study on calvarial osteoblastic cells isolated from Cx43+/- and Cx43+/+ mice.
Bone is a dynamic tissue that undergoes a precise remodeling process involving resorptive osteoclastic cells and bone-forming osteoblastic (OB) cells. The functional imbalance of either of these cell types can lead to severe skeletal diseases. The proliferation and differentiation of OB cells play a major role in bone development and turnover. These cellular processes are coordinated by connexin43 (Cx43)-based gap-junctional intercellular communication (GJIC) and by soluble factors such as endothelin-1 (ET-1). We have used the Cx43 heterozygous (Cx43(+/-)) murine model to study the possible cross-talk between Cx43 and ET-1 in cultured calvarial OB cells. On microcomputed tomographic analysis of 3-day-old pups, Cx43(+/-) mice showed hypomineralized calvaria in comparison with their Cx43(+/+) littermates. Characterization of cultured OB cells clearly demonstrated the effect of the partial deletion of the Cx43 gene on its expression, on GJIC, and subsequently on OB differentiation. In this model, ET-1 (10(-8) M) lost its mitogenic action in Cx43(+/-) OB cells compared with Cx43(+/+) cells. Moreover, a correlation between the inhibition of cell differentiation by ET-1 and the decreased amount and function of Cx43 was found in Cx43(+/+) OB cells but not in their Cx43(+/-) counterparts. Thus, as Cx43 is linked to OB differentiation, our data indicate that this mitogenic ET-1 peptide has pronounced effects on fully differentiated OB cells. With respect to roles in mechanotransduction and OB differentiation, Cx43 might modulate osteoblastic sensitivity to soluble factors.
Geneau
Graziello
G
Institut de Physiologie et Biologie Cellulaires, University of Poitiers, CNRS UMR 6187, 86022, Poitiers Cedex, France.
Lamiche
Coralie
C
Niger
Corinne
C
Strale
Pierre-Olivier
PO
Clarhaut
Jonathan
J
Defamie
Norah
N
Debiais
Françoise
F
Mesnil
Marc
M
Cronier
Laurent
L
D000818:Animals; D001851:Bone Diseases, Metabolic / Q000235:genetics; D016723:Bone Remodeling / Q000187:drug effects / Q000235:genetics; D002113:Calcification, Physiologic / Q000235:genetics; D002450:Cell Communication / Q000187:drug effects / Q000235:genetics; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics*; D002455:Cell Division / Q000235:genetics; D049109:Cell Proliferation; D018031:Connexin 43 / Q000235:genetics / Q000378:metabolism*; D019332:Endothelin-1 / Q000378:metabolism* / Q000494:pharmacology; D017629:Gap Junctions / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D006131:Growth Inhibitors / Q000378:metabolism / Q000494:pharmacology; D040542:Mechanotransduction, Cellular / Q000187:drug effects / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009924:Organ Culture Techniques; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism*; D010012:Osteogenesis / Q000187:drug effects / Q000235:genetics*; D012886:Skull / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology; D055114:X-Ray Microtomography
D018031:Connexin 43; D019332:Endothelin-1; C543076:GJA1 protein, mouse; D006131:Growth Inhibitors