Wnt signaling in bone formation and its therapeutic potential for bone diseases
Jeong Hwan Kim,Xing Liu,Jinhua Wang,Xiang Chen,Hongyu Zhang,Stephanie H. Kim,Jing Cui,Ruidong Li,Wenwen Zhang,Yuhan Kong,Jiye Zhang,Wei Shui,Joseph D. Lamplot,Mary Rose Rogers,Chen Zhao,Ning Wang,Prashant Rajan,Justin Tomal,Joseph Statz,Ningning Wu,Hue H. Luu,Rex C. Haydon,Tong-Chuan He +22 more
TLDR
The present review discusses the role of the Wnt signaling pathway in osteogenesis and examines its targeted therapeutic potential and indicates it requires cautious approach due to risks of tumorigenesis.Abstract:
The Wnt signaling pathway plays an important role not only in embryonic development but also in the maintenance and differentiation of the stem cells in adulthood. In particular, Wnt signaling has been shown as an important regulatory pathway in the osteogenic differentiation of mesenchymal stem cells. Induction of the Wnt signaling pathway promotes bone formation while inactivation of the pathway leads to osteopenic states. Our current understanding of Wnt signaling in osteogenesis elucidates the molecular mechanisms of classic osteogenic pathologies. Activating and inactivating aberrations of the canonical Wnt signaling pathway in osteogenesis results in sclerosteosis and osteoporosis respectively. Recent studies have sought to target the Wnt signaling pathway to treat osteogenic disorders. Potential therapeutic approaches attempt to stimulate the Wnt signaling pathway by upregulating the intracellular mediators of the Wnt signaling cascade and inhibiting the endogenous antagonists of the pathway. Antibodies against endogenous antagonists, such as sclerostin and dickkopf-1, have demonstrated promising results in promoting bone formation and fracture healing. Lithium, an inhibitor of glycogen synthase kinase 3β, has also been reported to stimulate osteogenesis by stabilizing β catenin. Although manipulating the Wnt signaling pathway has abundant therapeutic potential, it requires cautious approach due to risks of tumorigenesis. The present review discusses the role of the Wnt signaling pathway in osteogenesis and examines its targeted therapeutic potential.read more
Citations
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Notch Signaling Augments BMP9-Induced Bone Formation by Promoting the Osteogenesis-Angiogenesis Coupling Process in Mesenchymal Stem Cells (MSCs).
Junyi Liao,Qiang Wei,Yulong Zou,Jiaming Fan,Dongzhe Song,Jing Cui,Wenwen Zhang,Yunxiao Zhu,Chao Ma,Xue Hu,Xiangyang Qu,Liqun Chen,Xinyi Yu,Zhicai Zhang,Claire Q.F. Wang,Chen Zhao,Zongyue Zeng,Ruyi Zhang,Shujuan Yan,Tingting Wu,Xingye Wu,Yi Shu,Jiayan Lei,Yasha Li,Hue H. Luu,Michael J. Lee,Russell R. Reid,Guillermo A. Ameer,Jennifer Moriatis Wolf,Tong-Chuan He,Wei Huang +30 more
TL;DR: It’s conceivable that simultaneous activation of the BMP9 and Notch pathways should efficiently couple osteogenesis and angiogenesis of MSCs for successful bone tissue engineering.
Journal ArticleDOI
TGF-β/BMP signaling and other molecular events: regulation of osteoblastogenesis and bone formation
TL;DR: Accumulating evidence indicates that Runx2 is the key integrator, whereas Hh is a possible modulator, miRNAs are regulators, and β-catenin is a mediator/regulator within the extensive intracellular network.
Journal ArticleDOI
Wnt/β-catenin signaling plays an ever-expanding role in stem cell self-renewal, tumorigenesis and cancer chemoresistance
Maryam K. Mohammed,Connie Shao,Jing Wang,Qiang Wei,Xin Xin Wang,Zachary J Collier,Shengli Tang,Hao Liu,Fugui Zhang,Jiayi Huang,Dan Guo,Minpeng Lu,Feng Liu,Jianxiang Liu,Chao Ma,Lewis L. Shi,Aravind Athiviraham,Tong-Chuan He,Michael J Lee +18 more
TL;DR: An organized collection of evidence implicating Wnt signaling in tumorigenesis and chemoresistance is presented to facilitate the pursuit of Wnt pathway modulators that may improve outcomes of cancers in which WNT signaling contributes to aggressive disease and/or treatment resistance.
Journal ArticleDOI
The evolving roles of canonical WNT signaling in stem cells and tumorigenesis: implications in targeted cancer therapies
Ke Yang,Xin Wang,Hongmei Zhang,Hongmei Zhang,Zhongliang Wang,Zhongliang Wang,Guoxin Nan,Guoxin Nan,Yasha Li,Yasha Li,Fugui Zhang,Fugui Zhang,Maryam K. Mohammed,Rex C. Haydon,Hue H. Luu,Yang Bi,Yang Bi,Tong-Chuan He,Tong-Chuan He +18 more
TL;DR: This review is intended to serve as a refresher of the current understanding about the physiologic and pathogenic roles of WNT/β-catenin signaling pathway, and to outline potential therapeutic opportunities by targeting the canonical WNT pathway.
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