Open AccessBMP‐9‐induced osteogenic differentiation of mesenchymal progenitors requires functional canonical Wnt/β‐catenin signalling
Author(s) -
Tang Ni,
Song WenXin,
Luo Jinyong,
Luo Xiaoji,
Chen Jin,
Sharff Katie A.,
Bi Yang,
He BaiCheng,
Huang JiaYi,
Zhu GaoHui,
Su YuXi,
Jiang Wei,
Tang Min,
He Yun,
Wang Yi,
Chen Liang,
Zuo GuoWei,
Shen Jikun,
Pan Xiaochuan,
Reid Russell R.,
Luu Hue H.,
Haydon Rex C.,
He TongChuan
Publication year - 2009
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/j.1582-4934.2008.00569.x
Subject(s) - bone morphogenetic protein 2 , microbiology and biotechnology , chemistry , runx2 , wnt signaling pathway , osteoblast , mesenchymal stem cell , bone morphogenetic protein , gene knockdown , osteocalcin , beta catenin , alkaline phosphatase , biology , signal transduction , in vitro , biochemistry , apoptosis , gene , enzyme
Bone morphogenetic protein 9 (BMP‐9) is a member of the transforming growth factor (TGF)‐β/BMP superfamily, and we have demonstrated that it is one of the most potent BMPs to induce osteoblast differentiation of mesenchymal stem cells (MSCs). Here, we sought to investigate if canonical Wnt/β‐catenin signalling plays an important role in BMP‐9‐induced osteogenic differentiation of MSCs. Wnt3A and BMP‐9 enhanced each other’s ability to induce alkaline phosphatase (ALP) in MSCs and mouse embryonic fibroblasts (MEFs). Wnt antagonist FrzB was shown to inhibit BMP‐9‐induced ALP activity more effectively than Dkk1, whereas a secreted form of LPR‐5 or low‐density lipoprotein receptor‐related protein (LRP)‐6 exerted no inhibitory effect on BMP‐9‐induced ALP activity. β‐Catenin knockdown in MSCs and MEFs diminished BMP‐9‐induced ALP activity, and led to a decrease in BMP‐9‐induced osteocalcin reporter activity and BMP‐9‐induced expression of late osteogenic markers. Furthermore, β‐catenin knockdown or FrzB overexpression inhibited BMP‐9‐induced mineralization in vitro and ectopic bone formation in vivo , resulting in immature osteogenesis and the formation of chondrogenic matrix. Chromatin immunoprecipitation (ChIP) analysis indicated that BMP‐9 induced recruitment of both Runx2 and β‐catenin to the osteocalcin promoter. Thus, we have demonstrated that canonical Wnt signalling, possibly through interactions between β‐catenin and Runx2, plays an important role in BMP‐9‐induced osteogenic differentiation of MSCs.