Osteoprotegerin differentially regulates protease expression in osteoclast cultures |
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Authors: | Wittrant Y Couillaud S Theoleyre S Dunstan C Heymann D Rédini F |
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Institution: | Faculté de Médecine, Laboratoire de Physiopathologie de la Résorption Osseuse, 1 rue Gaston Veil, 44035 Nantes cedex 01, France. |
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Abstract: | Cysteine proteases and matrix metalloproteinases (MMPs) are important factors in the degradation of organic matrix components of bone. Osteoprotegerin (OPG) is an osteoblast-secreted decoy receptor that inhibits osteoclast differentiation and activation. This study investigated the direct effects of human OPG on cathepsin K, MMP-9, MMP-2, and tissue inhibitors of metalloproteinases (TIMP1 and TIMP2) expressed by purified rabbit osteoclasts. The expression of two osteoclast markers, namely tartrate-resistant acid phosphatase (TRAP) and cathepsin K, was inhibited by 100 ng/mL hOPG, whereas MMP-9 expression was enhanced. Gelatinase activities were measured using a zymographic assay, and hOPG was shown to enhance both pro-MMP-9 and MMP-2 activities. Concomitantly, TIMP1 expression was greatly stimulated by hOPG, whereas TIMP2 mRNA levels were not modulated. Overall, these results show that hOPG regulates the proteases produced by purified osteoclasts differentially, producing a marked inhibitory effect on the expression of cathepsin K, the main enzyme involved in bone resorption. |
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Keywords: | Osteoclast Bone resorption Osteoprotegerin Metalloproteinases Tissue inhibitors of metalloproteinases Cathepsin K |
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