Gene Discovery

Thursday, February 6, 2014

Gene discovery may aid treatment of osteoporosis and osteogenesis imperfecta

14-year-old boy participates in study

Children whose bodies do not generate sufficient bone mass encounter quality-of-life musculoskeletal issues. These issues, such as fragility fractures, occur throughout their lifetime.    

Researchers at Orthopaedic Institute for Children (OIC), in alliance with UCLA, and their colleagues from around the world,  have identified two skeletal diseases associated with atypical forms of WNT 1, a protein that influences bone formation and maintenance. Their findings may lead to eventual therapies for treating and/or preventing early onset osteoporosis and osteogenesis imperfecta.

OIC researchers Deborah Krakow, M.D. and Daniel H. Cohn, Ph.D. used a genetic approach to identify a key WNT molecule involved in the signaling processes essential for regulating normal skeletal development and bone mass. Drs. Krakow and Cohn are co-authors on a paper about the research that was recently published in the New England Journal of Medicine. To view full study click here.

The study found that in ten family members with inherited early-onset osteoporosis, a variation in the WNT 1 protein was associated with the disease, while, in a second family, a WNT 1 mutation was identified in two siblings with recessive osteogenesis imperfecta. In vitro and in a mouse model, the abnormal forms of the protein markedly reduced WNT1 signaling and diminished bone formation.

The work provides direct evidence in mice that WNT 1 is central to the successful initiation of bone mineralization.

"Identifying this molecule may ultimately help identify and track potential issues with skeletal health and identify targets for therapies for osteoporosis and OI," notes Dr. Cohn.

"This discovery opens up the possibility of developing treatments based on altering WNT signaling in bone," says Dr. Krakow.

Committed to finding better ways to treat and/or cure osteoporosis, osteogenesis imperfecta and skeletal dysplasias, OIC and the Krakow and Cohn laboratories are continuing innovative research on a molecular basis.

If you would like to support OIC research initiatives, please click here to give online or contact Michael Sullivan, Vice President of the OIC Foundation, at