Proper Fhl1 expression as Wnt signaling is required for chondrogenesis of ATDC5 cells

Abstract

Wnt signaling is well known playing dual roles during chondrogenesis. The overexpression of Fhl1 (Four-and-a-half LIM domain 1) induces myotube formation as a downstream event of Wnt signaling. Because Fhl1 is widely expressed in other mesenchyme-derived tissues, including chondrocytes, we investigated the role of Fhl1 in chondrogenesis and its relationship with Wnt signaling. We found that the expression of Fhl1 can be enhanced by β-catenin and LiCl (Lithium chloride) in chondrogenic ATDC5 cells. Overexpression of Fhl1 as well as canonical Wnt signaling inhibits chondrogenesis of ATDC5 cells. Moreover, shRNA-mediated knockdown of Fhl1 expression also inhibited ATDC5 cell differentiation, and this result is resembled to the mutant phenotype caused by deletion of β-catenin as was described previously. Because the endogenous Fhl1 expression remains constant during the middle and late phases of chondrogenesis, we propose that proper Fhl1 expression is necessary for the chondrogenic differentiation of ATDC5 cells and altered Fhl1 expression serves as an aberrant Wnt signal that impedes chondrogenesis.