The promise of canonical Wnt signaling modulators in enhancing bone repair.
The skeleton is vitally important for support, mechanical function and protection of internal organs. Over the last few decades, the molecular mechanisms by which bones develop and repair themselves have been the subject of intense research throughout the world. Particular attention has been paid to mesenchymal progenitors and the regulation of their differentiation to osteoblasts, the cells that build and repair bone. One of the major findings of these studies is that positive signaling by the canonical wingless (Wnt) pathway in mesenchymal progenitor cells is critical for the differentiation of the progenitors into osteoblasts. The subject of this review focuses on how perturbations of the Wnt pathway can adversely affect osteogenesis in disease and also, how pharmaceutical modulators of the Wnt pathway may be employed in the future to inhibit degenerative diseases of the bone and enhance repair.
Gregory
Carl A
CA
Center for Gene Therapy and Department of Medicine, Tulane University Health Sciences Center, 1430 Tulane Avenue, New Orleans, LA 70112, USA. cgregory@tulane.edu
Green
Angela
A
Lee
Narae
N
Rao
Ashwin
A
Gunn
William
W
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D050071:Bone Density Conservation Agents / Q000494:pharmacology; D001847:Bone Diseases / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D001861:Bone Regeneration / Q000187:drug effects; D001842:Bone and Bones / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002454:Cell Differentiation; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism; D010012:Osteogenesis; D047495:PPAR gamma / Q000037:antagonists & inhibitors / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D051153:Wnt Proteins / Q000378:metabolism*
D000906:Antibodies; D050071:Bone Density Conservation Agents; C501126:DKK1 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D047495:PPAR gamma; D047428:Protein Kinase Inhibitors; D051153:Wnt Proteins; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3