The Osteoarthritis Initiative: The Power and Potential of Interdisciplinary Research

Adapted from the Spring 2013 issue of Discovery to Recovery

Osteoarthritis (OA), the painful and often debilitating disease in which cartilage breaks down until it can no longer serve its function as a cushion between the bones, is the most common underlying condition that brings patients to Hospital for Special Surgery. For decades, our scientists have conducted research to better understand the disease. While the symptoms of OA are well-known, scientists are still uncovering its root causes. The only cure for advanced OA remains joint replacement.

An interdisciplinary team of HSS scientists and physicians investigates how OA works, with the goal of developing methods of prevention and, ultimately, a cure. More than 350 clinicians, clinical investigators, and basic scientists across the Department of Orthopedics, the Division of Rheumatology, and the Research Division at HSS are addressing OA on some level, and 15 OA-related research grants are well under way.

In recent years, the Hospital’s OA research efforts have been formalized through the leadership support of the Starr Foundation, Li Ka Shing Foundation, National Institutes of Health, and many other private and public donors who have enabled HSS to establish the Osteoarthritis Initiative – an integrated basic, translational, and clinical research program to advance OA research.

Uncovering the Biology of Joint Tissues

Mary Goldring, PhD, director of the Laboratory for Cartilage Biology and the Ira W. DeCamp Fellow in Musculoskeletal Genetics, examines genetic activity in cartilage along a continuum from normal tissue to progressive OA.

Her goal is to identify targets for therapy to block damage to the cartilage and promote its repair. “We are trying to understand the molecular biology of the cells within the cartilage under normal conditions and how the activities of those cells change when cartilage is damaged,” says Dr. Goldring, who is the recipient of a Director’s Award from the NIH. Her laboratory has uncovered new roles of genes not previously known to act in cartilage, and she and her colleagues are studying the genetic mechanisms that promote the progression of OA.

This research is important because understanding how genes work in a disease is the first step toward developing therapies to prevent the disease from progressing. Follow-up studies may lead to the identification of critical targets for therapy to block the initiation of cartilage damage or even promote cartilage repair with cell-based tissue-engineering approaches.

The Multiple Roles of MRI

Today’s magnetic resonance imaging (MRI) techniques in orthopedics – many developed by Hollis G. Potter, MD, chief, Division of MRI and the Coleman Chair in MRI Research – have made it possible for the first time to identify deficiencies in joint tissue following an injury that are associated with the very early onset of osteoarthritis.

With support from the NIH, Dr. Potter uses non-invasive MRI to explore the structural components that allow articular and fibrocartilage to withstand applied force, called “load.” “If you jump from a height onto a flexed knee, such as in a rebound in basketball, you are loading the cartilage in that knee,” explains Dr. Potter.

“Having insight into the ultrastructure of the cartilage is essential in diagnosing OA resulting from trauma or a predisposition to early OA. These imaging techniques also allow us to evaluate the health of the cartilage following surgical repair without performing a surgical biopsy.”

Exploring Novel Materials for OA Treatment

As a clinician-scientist, Scott A. Rodeo, MD, co-chief emeritus of the Sports Medicine Institute, repairs his patients’ soft tissue injuries. He then takes the challenges he faces in the clinical setting into his basic science laboratory, where he and his colleagues investigate the biology of cartilage.

In one such project, they are evaluating lubricin, an important molecule produced in the joint by cells on the surface of cartilage. “Lubricin adds lubricating capacity to normal joints, helping to reduce wear on cartilage,” says Dr. Rodeo. “In arthritis, this material is often deficient.”

Dr. Rodeo’s lab is collaborating with the Department of Biomedical Engineering at Cornell University to study synthetic materials that are lubricin-like, with the hope that they will help reduce wear on cartilage. If successful, the potential exists for developing a simple, injectable therapy that could help delay the onset of OA.

Poised to Transform OA Treatment

“Public health data indicate that the prevalence, impact, and economic consequences of osteoarthritis are expected to rise dramatically over the next several decades,” says Steven R. Goldring, MD, chief scientific officer and the Richard L. Menschel Research Chair. “HSS provides a wonderful interactive environment in which dialogues between scientists and physicians help to define the major clinical problems associated with OA and how research can address them.”

Read the full Discovery to Recovery Spring 2013 issue.

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