Hotline Archive - Cartilage Growth Factor (Tgf-ß) in Osteoarthritis
March 1994
Osteoarthritis is characterized first by focal defects in cartilage and, later, by diffuse erosive cartilage loss. Treatment is currently symptomatic rather than specific. A number of investigators are engaged in studies of so-called "chondroprotective agents" - agents which prevent, retard or reverse anatomic changes in the disease process. Alternative chondroprotective mechanisms include inhibition of cartilage degradative metalloproteases, or stimulation of chondrocyte proliferation and matrix synthesis. Drs. Ernst Hunziker of the University of Bern, Switzerland, and Lawrence Rosenberg of Montefiore Medical Center, New York, described repair of experimentally induced focal partial-thickness defects in the cartilage of New Zealand white rabbits utilizing transforming growth factor-ß (TGF-ß). The studies, reported at the 40th Annual Meeting of the Orthopaedic Research Society in New Orleans, compared healing in response to fibrinogen alone (controls); fibrinogen and free-TGF-ß in low concentrations; and fibrinogen, free-TGF-ß and liposome-encapsulated TGF-ß (condrogeneron) in high concentrations released slowly over time. Animals were examined at intervals up to 12 months after surgery. In animals treated with fibrinogen alone, no new cartilage formed and there was no improvement in the cartilage defects. The defects in the group treated with fibrinogen and free-TGF-ß exhibited increased cellularity, with repair cells migrating from the synovial membrane across the articular cartilage surface defect into the fibrin clot. These cells retained the morphology of fibroblasts and did not differentiate into chondrocytes or form cartilage. Treatment with free-TGF-ß and liposome-encapsulated TGF-ß was associated with cartilage repair which resembled normal hyaline cartilage; its integrity was found to persist at one year after surgery. TGF-ß released at high concentration from liposomes appeared to promote cartilage proliferation and differentiation .
The investigations are a prototype of a number of similar studies being carried out by other investigators utilizing not only growth factors such as TGF-ß or insulin-like growth factor (IGF-1), but also using cellular replacement derived from cartilage, periosteum, or bone marrow mesenchymai stem cells. These creative investigations, based on logical postulates regarding cartilage repair mechanisms, support the concept that such reparative techniques can be utilized at some future time. At present these treatments have not been studied in humans and are not approved or available for treatment of osteoarthritis. Caveats related to their clinical use include the ability to retain reparative materials within osteoarthritic defects; safety and tolerance; consistency of cartilaginous response and duration of architectural and biomechanical integrity; and confirmatory studies in other animal species. Notwithstanding these caveats, these investigations provide optimism for development of specific approaches to the treatment of osteoarthritis.
Prepared by Roland W. Moskowitz, MD, Professor of Medicine, Director, Division of Rheumatic Diseases, Case Western Reserve University, Cleveland, Ohio, with Richard S. Panush, MD, and Robert Thoburn, MD, editors.
This Hotline was solicited by the American College of Rheumatology Communications and Marketing Group as an informational service to members. This Hotline does not represent a position statement of the College.
3/1/94
