Thickening of the subchondral plate alters the effects of mechanical loading on articular cartilage. Changes in subchondral blood flow and intraosseous pressure have been implicated in OA disease progression [82,134,217]. As OA develops, new osteochondrophyte structures, named osteophytes, make their appearance. Osteophyte formation occurs commonly at the junction of the periosteum and the activated synovium (synovitis) [79,209]. Osteo-phytes are found at the margin of cartilage and bone, but the bone content of osteophytes is higher. Bone formation within the cartilaginous matrix of osteophytes appears to recapitulate endochondral ossification in the course of development. Angiogenesis may contribute to osteophyte growth [18,99,239,241]. Osteophytes are considered stabilizing structures that redistribute biomechanical forces during the stand-up position and when persons walk. Osteo-phytes, however, limit the natural motion of the joint  and have been associated with pain. They thus play a beneficial or harmful role . Scintigraphy is a good tool to identify growing, active osteophytes whose presence may indicate joint disintegration [56,232]. Osteophytes are associated with an inflammation of the synovial membrane. Furthermore, some growth factors such as TGF-P, basic fibroblast growth factor (bFGF), or BMP-2 injected directly in the joint cannot be used to repair an osteochondral defect, because they induce synovial inflammation and the appearance of osteophytes [162,229,230]. In contrast, injection of hepatocyte growth factor (HGF) alone or of bFGF in combination with hyaluronic acid does not activate the synovium, nor does it generate osteo-phytes [162,237]. Synovial lining macrophages have recently been shown to mediate osteo-phyte formation during experimental OA, because macrophage depletion dramatically abolished osteophyte formation . Although the mechanism is not understood, one can hypothesize that some macrophages from the synovial membrane differentiate into osteo-clasts, releasing growth factors bound to the extracellular matrix of bone, and induce the osteochondral process that leads to osteo-phyte formation. Indeed, macrophages in the synovial membrane can differentiate into osteoclasts .
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