engleski

Immunohistochemical study of the BMPs and their extracellular antagonists in osteoarthritic human knee joint

The osteophytes are bone spurs overgrowing the edge of the articular cartilage during the course of osteoarthritis (OA). The cellular mechanism of their development and growth resembles the intramembranous and endochondral bone development during embrional and postnatal normal bone development, growth, modeling, remodeling and repair. The role of BMPs in bone development and metabolism is well documented and the members of the BMPs molecular network were recognized as important factors which could modulate new bone development and growth of osteophytes. The purpose of this study is to analyze the cooexpression of the most potent osteoinductive members of the BMP family (BMP-2, -4 and -7) and their extracellular antagonists gremlin, noggin, chordin, follistatin in order to establish their role during degenerative process of the synovial joints and growth of osteophyte. In this study, the BMP-2, BMP-4, BMP-7, gremlin, noggin, chordin, follistatin expressions were analyzed in joint tissues from OA patients and from healthy individuals by immunohistochemistry and Western blot. The immunohistochemistry showed different localization pattern of BMPs and BMP extracellular antagonists expressions in OA vs. normal joint tissues. In osteophyte, BMP-2 was not detected, while BMP-4 and BMP-7 were positive in hypertrophyc chondrocytes and osteocytes at the sites of endochondral bone development. BMP-7 was strongly positive, while BMP-4 was negative in synovial membrane of OA joints. Gremlin, chordin and noggin were found in chondrocytes, osteoblasts of the osteophytic bone and synovial epithelium, while follistatin was found in chondrocytes, blood vessels and synovial epithelium. Our result demonstrate the significant differences in BMPs and their antagonists expression in normal tissues compare to joint tissue affected by OA and revealed how molecular balance of the local growth factors such as BMPs and their antagonists could be disturbed during degenerative processes. Also, these findings suggest the potent role of these molecular factors in pathogenesis of the OA and/or during growth and development of the human knee joint osteophytes.

BMP ; gremlin ; noggin ; chordin ; follistatin ; osteophytes

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