Osteoarthritis Onset, Progression Mechanisms Explored with ARRA Funding

At the Hospital for Special Surgery in New York City, Mary Goldring, Ph.D., and her colleagues there and at other institutions around the country are undertaking what they believe is a major step in defining the molecular mechanisms behind the onset and progression of osteoarthritis (OA), a disease in which the cartilage that cushions bones in joints wears away. According to Dr. Goldring, their work funded by the American Recovery and Reinvestment Act (ARRA) through the National Institute of Arthritis and Musculoskeletal and Skin Diseases' may lead to the identification of critical targets for therapy to block OA cartilage damage and promote its repair.

Photo ID: Mary Goldring, Ph.D.

"We think that stress- or inflammation-induced signals contribute not only to irreversible joint damage in OA," says Dr. Goldring, "but to the onset of the disease, where cartilage cells depart from their normal pattern of growth and differentiation." The scientists are studying three different mouse models of OA that reflect different changes in the function and physiology of chondrocytes, which are the cells residing in the cartilage. They are seeking to identify key regulatory molecules, including transcription factors and signaling kinases, that may contribute to stress and differentiation in cartilage cells. Advanced proteomic (protein) and genomic (gene) approaches are being used to map the signaling pathways and molecular regulators that impact gene expression during OA onset and progression. Among the critical targets are cartilage-degrading enzymes such as matrix metalloproteinase (MMP)-13, an enzyme that breaks down collagen, a protein found in abundance in cartilage. Once the investigators have defined the key pathways and factors at work in mouse OA, they will be able to compare them with existing genomic or proteomic datasets from human OA, and uncover clinically relevant therapeutic targets.

The Hospital for Special Surgery is joined in the work by scientists at Stony Brook (N.Y.) University, San Diego State University and the Harvard School of Dental Medicine. ARRA funding has proved critical to her team's efforts, says Dr. Goldring, allowing new research staff to be hired and continuing the work of at least one research technician at each collaborating institution. In addition, the support has enabled the investigators to expand their mouse facilities and create at least one new OA mouse model. "ARRA's investment in our project," remarks Dr. Goldring, "is enabling us to make significant progress against a condition that affects millions of Americans."

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The activity above is being funded through the American Recovery and Reinvestment Act (ARRA). More information about the National Institutes of Health's ARRA grant funding opportunities can be found at https://grants.nih.gov/recovery/. To track the progress of HHS activities funded through the ARRA, visit http://www.hh.gov/rescovery/. To track all federal funds provided through the ARRA, visit http://www.recovery.gov.