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The pro‐osteogenic action of β‐catenin requires interaction with BMP signaling, but not Tcf/Lef transcriptional activity
Author(s) -
Salazar Valerie S.,
Mbalaviele Gabriel,
Civitelli Roberto
Publication year - 2008
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.21679
Subject(s) - microbiology and biotechnology , chemistry , beta catenin , action (physics) , bmpr2 , catenin , signal transduction , cancer research , bone morphogenetic protein , wnt signaling pathway , biology , biochemistry , physics , gene , quantum mechanics
The role of β‐catenin in skeletal development and osteogenic cell differentiation is well established, but the molecular mechanisms attending these effects remain largely unknown. We conducted a structure/function analysis of β‐catenin to gain further insights on these mechanisms. Retroviral transduction of a full‐length, constitutively active β‐catenin mutant inhibited adipogenesis and stimulated osteoblast differentiation from multipotent embryonic fibroblasts (C3H10T1/2). However, N‐terminal truncated β‐catenin mutants with weak Tcf/Lef activity retained their pro‐osteogenic action, as did a constitutively stabilized mutant lacking the C‐terminal Tcf/Lef transactivation domain. Importantly, this Tcf/Lef‐defective β‐catenin did not suppress adipogenesis, and even elicited spontaneous adipogenesis when expressed in cells cultured in osteogenic conditions. Thus, Tcf/Lef transcriptional activity of β‐catenin is critical for inhibition of adipogenesis, while it is dispensable for its pro‐osteogenic effect. BMP‐2 greatly enhanced both osteogenesis and adipogenesis in the presence of the C‐terminally truncated mutant, though it selectively enhanced only osteoblast differentiation in cells transduced with the full‐length, Tcf/Lef active β‐catenin mutant. C3H10T1/2 cells produce BMP‐4, and inhibition of endogenous BMP signaling by Noggin curtailed osteogenic differentiation by constitutively active β‐catenin. Therefore, BMP signaling must be active for full induction by β‐catenin of osteogenic differentiation from multipotent precursors. These data suggest that cooperative interactions between β‐catenin and BMP signaling systems drive osteoblast cell fate specification and differentiation. J. Cell. Biochem. 104: 942–952, 2008. © 2008 Wiley‐Liss, Inc.