Regulation of osteoclast protease expression by RANKL |
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Authors: | Wittrant Y Theoleyre S Couillaud S Dunstan C Heymann D Rédini F |
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Institution: | Laboratoire de Physiopathologie de la Résorption Osseuse et Thérapie des Tumeurs Osseuses Primitives EE 99-01, Faculté de Médecine, Nantes, France. |
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Abstract: | Receptor activator of NF-kappaB ligand (RANKL) is essential for osteoclast (OC) differentiation/activation and functions through its receptor RANK at the surface of the osteoclastic cells. This study investigated for the first time the direct effects of hRANKL on protease/protease inhibitor expressions and protease activities in purified rabbit osteoclast cultures, using semi-quantitative RT-PCR, gelatin zymography, and enzymatic assays. RANKL was shown to exert in vitro pro-resorptive effects by increasing osteoclast marker expressions (Tartrate resistant acid phosphatase (TRAP) and cathepsin K), MMP-9 expression, and pro-MMP-9 activity and by diminishing TIMP-1 expression, leading to an up-regulation of the MMP-9/TIMP-1 ratio. |
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Keywords: | RANKL Osteoclasts Bone resorption Metalloproteinase |
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