title: Osteoprotegerin differentially regulates protease expression in osteoclast cultures.
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.
authors.affiliation: Faculté de Médecine, Laboratoire de Physiopathologie de la Résorption Osseuse, 1 rue Gaston Veil, 44035 Nantes cedex 01, France.
authors.forename: Y
authors.initials: Y
authors.lastname: Wittrant
authors.forename: S
authors.initials: S
authors.lastname: Couillaud
authors.forename: S
authors.initials: S
authors.lastname: Theoleyre
authors.forename: C
authors.initials: C
authors.lastname: Dunstan
authors.forename: D
authors.initials: D
authors.lastname: Heymann
authors.forename: F
authors.initials: F
authors.lastname: Rédini
mesh_terms: D000135:Acid Phosphatase / Q000235:genetics; D000818:Animals; D000831:Animals, Newborn; D056657:Cathepsin K; D002403:Cathepsins / Q000235:genetics; D002478:Cells, Cultured; D017931:DNA Primers; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000502:physiology*; D006023:Glycoproteins / Q000502:physiology*; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D020782:Matrix Metalloproteinases / Q000235:genetics*; D010010:Osteoclasts / Q000201:enzymology*; D053244:Osteoprotegerin; D012333:RNA, Messenger / Q000235:genetics; D011817:Rabbits; D018160:Receptors, Cytoplasmic and Nuclear / Q000502:physiology*; D018124:Receptors, Tumor Necrosis Factor; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000235:genetics
chemical_list: D017931:DNA Primers; D006023:Glycoproteins; D053244:Osteoprotegerin; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; D011993:Recombinant Fusion Proteins; C506030:TNFRSF11B protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D000135:Acid Phosphatase; D002403:Cathepsins; C534130:CTSK protein, human; D056657:Cathepsin K; D020782:Matrix Metalloproteinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9