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Wnt3a and Wnt1 Enhance Myogenesis of C2C12 Myoblasts – Potential Mechanisms of Osteocyte to Muscle Cell Signaling
Author(s) -
Huang Jian,
Mo Chenglin,
Bonewald Lynda,
Brotto Marco
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.947.13
Subject(s) - myogenesis , wnt3a , wnt signaling pathway , c2c12 , myod , microbiology and biotechnology , signal transduction , myocyte , myogenic regulatory factors , chemistry , biology
We have proposed that muscle and bone communicate via biochemical factors that are reciprocally important for optimal function. WNTs are secreted by osteocytes and have a significant potential to directly influence muscle function. We showed that WNT3a enhanced myogenic differentiation at a concentration of as low as 0.5ng/ml, and stimulated β‐catenin translocation to the nucleus of C2C12 muscle cells. Now, we show that Wnts express in MLO‐Y4 osteocytes and 2T3 osteoblasts, and their expression is dramatically enhanced by fluid flow shear stress, suggesting a physiological role with increased activity for example. WNT3a promoted overexpression of myogenic markers ( MyoD , MyoG , MHC ), and downstream genes of the β‐catenin pathway ( Fhl1 and Numb ). Furthermore, WNT3a treated C2C12 cells demonstrated higher expression of Axin2 , Wnt5a , Gata3 and Adm , while the expression of Hey2 , Ifng , Icam1 , Tnf and Lrg1 decreased significantly. These genes represent the Wnt signaling pathway ( Axin2, Wnt5a ), JAK1, 3/Stat6 signaling pathway (Gata3 ), Hypoxia signaling pathway ( Adm ), Notch signaling pathway ( Hey2 ), NFκB signaling pathway ( Tnf, Ifng, Icam1 ) and the Stat3 signaling pathway ( Lrg1 ). These results suggest that WNT3a may function through these pathways to regulate C2C12 myoblast differentiation. Support: NIH‐NIA P01 AG039355 (LB, MB), and the Dale and Dorothy Thompson Endowment Fund (MB).