Regulation of osteoclast protease expression by RANKL.
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.
Wittrant
Y
Y
Laboratoire de Physiopathologie de la Résorption Osseuse et Thérapie des Tumeurs Osseuses Primitives EE 99-01, Faculté de Médecine, Nantes, France.
Theoleyre
S
S
Couillaud
S
S
Dunstan
C
C
Heymann
D
D
Rédini
F
F
D000135:Acid Phosphatase / Q000096:biosynthesis; D000818:Animals; D002352:Carrier Proteins / Q000502:physiology*; D056657:Cathepsin K; D002403:Cathepsins / Q000096:biosynthesis; D002454:Cell Differentiation; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D010450:Endopeptidases / Q000096:biosynthesis*; D007527:Isoenzymes / Q000096:biosynthesis; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D008562:Membrane Glycoproteins / Q000502:physiology*; D010010:Osteoclasts / Q000201:enzymology* / Q000378:metabolism; D053245:RANK Ligand; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000071681:Tartrate-Resistant Acid Phosphatase; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000096:biosynthesis; D015854:Up-Regulation
D002352:Carrier Proteins; D007527:Isoenzymes; D008562:Membrane Glycoproteins; D053245:RANK Ligand; D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase; D002403:Cathepsins; D010450:Endopeptidases; D056657:Cathepsin K; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9