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      Regulation of bone mass by Wnt signaling.

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          Abstract

          Wnt proteins are a family of secreted proteins that regulate many aspects of cell growth, differentiation, function, and death. Considerable progress has been made in our understanding of the molecular links between Wnt signaling and bone development and remodeling since initial reports that mutations in the Wnt coreceptor low-density lipoprotein receptor-related protein 5 (LRP5) are causally linked to alterations in human bone mass. Of the pathways activated by Wnts, it is signaling through the canonical (i.e., Wnt/beta-catenin) pathway that increases bone mass through a number of mechanisms including renewal of stem cells, stimulation of preosteoblast replication, induction of osteoblastogenesis, and inhibition of osteoblast and osteocyte apoptosis. This pathway is an enticing target for developing drugs to battle skeletal diseases as Wnt/beta-catenin signaling is composed of a series of molecular interactions that offer potential places for pharmacological intervention. In considering opportunities for anabolic drug discovery in this area, one must consider multiple factors, including (a) the roles of Wnt signaling for development, remodeling, and pathology of bone; (b) how pharmacological interventions that target this pathway may specifically treat osteoporosis and other aspects of skeletal health; and (c) whether the targets within this pathway are amenable to drug intervention. In this Review we discuss the current understanding of this pathway in terms of bone biology and assess whether targeting this pathway might yield novel therapeutics to treat typical bone disorders.

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          Author and article information

          Journal
          J Clin Invest
          The Journal of clinical investigation
          American Society for Clinical Investigation
          0021-9738
          0021-9738
          May 2006
          : 116
          : 5
          Affiliations
          [1 ] Musculoskeletal Research, Lilly Research Laboratories, Indianapolis, Indiana 462385, USA. krishnan_gary@lilly
          Article
          10.1172/JCI28551
          1451219
          16670761
          67b3551c-42ce-4ad3-848d-ee1d681513ec
          History

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