Targeting the Wnt signaling pathway to augment bone formation.
Recent discoveries in humans and mice have revealed that the Wnt (Wingless and Int-1) signaling pathway is responsible for a complex array of functions in maintaining bone homeostasis. The Wnt proteins are key modulators of mesenchymal lineage specification and regulate most aspects of osteoblast physiology and postnatal bone acquisition by controlling the differentiation and activity of osteoblasts and osteoclasts. Initial reports have indicated that activators of Wnt signaling are potent promoters of osteogenesis; however, systemic hyperactivation of the canonical Wnt pathway could potentially accelerate neoplastic transformation and subsequent tumor growth. Alternatively, recent investigations of natural soluble antagonists of Wnt signaling in bone suggest the possibilities of bone-specific therapies targeting the negative regulators of Wnt pathway, especially sclerostin. With this new knowledge, novel pharmacologic interventions that alter Wnt signaling are being evaluated for the management of osteoporosis. In this article, we briefly describe the Wnt signaling elements, their characterized role in bone, and summarize the current knowledge on the potential to enhance bone formation through the manipulation of Wnt signaling antagonists.
Shahnazari
Mohammad
M
Department of Medicine, UC Davis Medical Center, 4800 Second Avenue, Suite 2600, Sacramento, CA 95817, USA.
Yao
Wei
W
Corr
Maripat
M
Lane
Nancy E
NE
D048868:Adaptor Proteins, Signal Transducing; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D001842:Bone and Bones / Q000378:metabolism; D005819:Genetic Markers; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D010012:Osteogenesis / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D051153:Wnt Proteins / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D019485:Bone Morphogenetic Proteins; C501126:DKK1 protein, human; D005819:Genetic Markers; D036341:Intercellular Signaling Peptides and Proteins; C422903:SOST protein, human; D051153:Wnt Proteins