title: Expression of bone resorption genes in osteoarthritis and in osteoporosis.
abstract: Cathepsin K and MMP-9 are considered to be the most abundant proteases in osteoclasts. TRAP is a marker for osteoclasts, and there is increasing evidence of its proteolytic role in bone resorption. RANKL is a recently discovered regulator of osteoclast maturation and activity and induces expression of many genes. This study compared cathepsin K, MMP-9, TRAP, RANKL, OPG, and osteocalcin gene expression in the proximal femur of patients with osteoarthritis with that of patients with femoral neck fracture. Fifty-six patients undergoing arthroplasty because of osteoarthritis or femoral neck fracture were included in the study. Total mRNA was extracted from the bone samples obtained from the intertrochanteric region of the proximal femur. Real-time RT-PCR was used to quantify CTSK (cathepsin K), MMP-9 (matrix metalloproteinase 9), ACP5 (TRAP), TNFSF11 (RANKL), TNFRSF11B (OPG), and BGLAP (osteocalcin) mRNAs. The levels of mRNAs coding for MMP-9 and osteocalcin indicated higher expression in the osteoarthritic group (P = 0.011, P = 0.001, respectively), whereas RANKL expression and the ratio RANKL/OPG were both significantly lower in the osteoarthritic group than in the fracture group. Expression of cathepsin K, MMP-9, and TRAP relative to RANKL was significantly higher in the osteoarthritic group. Ratios of all three proteolytic enzymes relative to formation marker osteocalcin were higher in the fracture group. Gene expression of cathepsin K, MMP-9, TRAP, RANKL, OPG, and osteocalcin and the association between their mRNA levels pointed to higher bone resorption and bone formation in osteoarthritis, differences in balance between them, and differences in regulation of bone resorption in osteoarthritic and osteoporotic bone.
authors.affiliation: Department of Clinical Biochemistry, Faculty of Pharmacy, University of Ljubljana, Askerceva 7, SI-1000, Ljubljana, Slovenia.
authors.forename: Darja Bitenc
authors.initials: DB
authors.lastname: Logar
authors.forename: Radko
authors.initials: R
authors.lastname: Komadina
authors.forename: Janez
authors.initials: J
authors.lastname: Prezelj
authors.forename: Barbara
authors.initials: B
authors.lastname: Ostanek
authors.forename: Zoran
authors.initials: Z
authors.lastname: Trost
authors.forename: Janja
authors.initials: J
authors.lastname: Marc
mesh_terms: D000135:Acid Phosphatase / Q000235:genetics; D000368:Aged; D000369:Aged, 80 and over; D001862:Bone Resorption / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism; D056657:Cathepsin K; D002403:Cathepsins / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D007527:Isoenzymes / Q000235:genetics; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D010003:Osteoarthritis / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism; D015675:Osteocalcin / Q000235:genetics; D010024:Osteoporosis / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism; D053244:Osteoprotegerin / Q000235:genetics; D053245:RANK Ligand / Q000235:genetics; D000071681:Tartrate-Resistant Acid Phosphatase
chemical_list: D007527:Isoenzymes; D053244:Osteoprotegerin; D053245:RANK Ligand; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human; D015675:Osteocalcin; C000605510:ACP5 protein, human; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase; D002403:Cathepsins; C534130:CTSK protein, human; D056657:Cathepsin K; D020780:Matrix Metalloproteinase 9