Role of WNT Signaling in Bone Remodeling and Repair

Paul S. Issack, MD, PhD
Orthopaedic Trauma, Adult Reconstructive Surgery, and Metabolic Bone Diseases, Hospital for Special Surgery

David L. Helfet, MD
Orthopaedic Trauma Service, Hospital for Special Surgery

Joseph M. Lane, MD
Metabolic Bone Disease Service, Hospital for Special Surgery


Abstract
The Wnt genes encode a highly conserved class of signaling factors required for the development of several types of tissues including musculoskeletal and neural structures. There is increasing evidence that Wnt signaling is critical for bone mass accrual, bone remodeling, and fracture repair. Wnt proteins bind to cell-surface receptors and activate signaling pathways which control nuclear gene expression; this Wnt-regulated gene expression controls cell growth and differentiation. Many of the components of the Wnt pathway have recently been characterized, and specific loss-of-function or gain-of-function mutations in this pathway in mice and in humans have resulted in disorders of deficient or excess bone formation, respectively. Pharmacologically targeting components of the Wnt signaling pathway will allow for the manipulation of bone formation and remodeling and will have several orthopedic applications including enhancing bone formation in nonunion and osteoporosis and restricting pathologic bone formation in osteogenic tumors and heterotopic ossification.

This article appears in HSS Journal: Volume 4, Number 1.
View the full article at springerlink.com.


About the HSS Journal
HSS Journal, an academic peer-reviewed journal, is published twice a year, February and September, and features articles by internal faculty and HSS alumni that present current research and clinical work in the field of musculoskeletal medicine performed at HSS, including research articles, surgical procedures, and case reports.


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