Investigations in the Orthopaedic Research Unit have focused on defining the events that regulate gene expression during repair. New projects include the development of a model to study cartilage repair after injury or in degenerative and traumatic osteoarthritis, and investigations of the role of growth factors in the development of tendon adhesions. Studies of TGF-beta demonstrate that this factor is an important regulator of cell proliferation, differentiation and protein synthesis during fracture healing. TGF-beta stimulates changes in chondrocyte development and gene expression associated with chondrocyte maturation in the fracture callus in vitro. TGF-beta stimulated mesenchymal cell proliferation and differentiation into both osteoblasts and chondrocytes with subsequent synthesis of cartilage and bone matrix respectively in vivo. TGF-beta 1, but not TGF-beta 2, is synthesized at high levels in both human and rat fracture calluses. TGF-beta stimulates chondrocyte differentiation and an increase in chondrocyte-specific gene expression in cultured periosteal cells. Studies of cartilage explant cultures demonstrate that, in the absence of inflammatory and synovial influences, serum stimulates cartilage chondrocytes to proliferate, synthesize new matrix, and initiate a repair response. This repair response is duplicated by the administration of basis FGF, but not TGF-beta. Antibodies to TGF-beta, and PDGF stained the tendon and tendon sheath after laceration in a chicken model. Both TGF-beta and aFGF stimulated a biphasic increase in tenocyte proliferation. In contrast, PDGF stimulated a 3 to 5-fold increase in cell proliferation. TGF-beta stimulated a 6-fold increase in matrix synthesis by proline incorporation.

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National Institute of Arthritis and Musculoskeletal and Skin Diseases
United States
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