title: Wnts' fashion statement: from body stature to dysplasia.
abstract: Bone is constantly being made and remodeled to maintain bone volume and calcium homeostasis. Even small changes in the dosage, location and duration of int/Wingless (Wnt) signaling affect skeletal development and homeostasis. Wnt/β-catenin signaling controls cell fate determination, proliferation and survival by affecting a balance between bone-forming osteoblast and bone-resorbing osteoclast cell differentiation. During early skeletal development, Wnt/β-catenin signaling is required in directing mesenchymal progenitor cells toward the osteoblast lineage. Later, Wnt/β-catenin in chondrocytes of the growth plate promotes chondrocyte survival, hypertrophic differentiation and endochondral ossification. Gain- or loss-of-function mutations in the Wnt signaling components are causally linked to high or low bone mass in mice and humans. Inactivation of Wnt/β-catenin signaling leads to imbalance between bone formation and resorption because of accelerated osteoclastogenesis due to decline in the levels of osteoprotegerin (OPG) secreted by osteoblasts or directly via Frizzled 8 (Fzd8). In this review, we provide a landscape of the Wnt pathway components in influencing progenitor cell differentiation toward osteoblasts or osteoclasts under physiological conditions as well as pathological disorders resulting in various skeletal dysplasia syndromes.
authors.affiliation: Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health , Bethesda, MD, USA.
authors.forename: Deepti
authors.initials: D
authors.lastname: Malhotra
authors.affiliation: Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health , Bethesda, MD, USA.
authors.forename: Yingzi
authors.initials: Y
authors.lastname: Yang