Expression of bone resorption genes in osteoarthritis and in osteoporosis

被引:141
作者
Logar, Darja Bitenc
Komadina, Radko
Prezelj, Janez
Ostanek, Barbara
Trost, Zoran
Marc, Janja
机构
[1] Univ Ljubljana, Fac Pharm, Dept Clin Biochem, SI-1000 Ljubljana, Slovenia
[2] Gen & Teaching Hosp Celje, Dept Traumatol, Celje, Slovenia
[3] Ctr Clin, Dept Endocrinol & Metab Dis, Ljubljana, Slovenia
关键词
cathepsin K; MMP-9; TRAP; RANKL; osteoprotegerin;
D O I
10.1007/s00774-007-0753-0
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
引用
收藏
页码:219 / 225
页数:7
相关论文
共 36 条
[1]   Increased RANKL/OPG mRNA ratio in iliac bone biopsies from women with hip fractures [J].
Abdallah, BM ;
Stilgren, LS ;
Nissen, N ;
Kassem, M ;
Jorgensen, HRI ;
Abrahamsen, B .
CALCIFIED TISSUE INTERNATIONAL, 2005, 76 (02) :90-97
[2]   A scrutiny of matrix metalloproteinases in osteoclasts:: evidence for heterogeneity and for the presence of MMPs synthesized by other cells [J].
Andersen, TL ;
Ovejero, MD ;
Kirkegaard, T ;
Lenhard, T ;
Foged, NT ;
Delaissé, JM .
BONE, 2004, 35 (05) :1107-1119
[3]  
Antoniades L, 2000, ARTHRITIS RHEUM, V43, P1450, DOI 10.1002/1529-0131(200007)43:7<1450::AID-ANR6>3.0.CO
[4]  
2-6
[5]  
Arden NK, 1999, ARTHRITIS RHEUM, V42, P1378, DOI 10.1002/1529-0131(199907)42:7<1378::AID-ANR11>3.0.CO
[6]  
2-I
[7]   Osteoclast signalling pathways [J].
Blair, HC ;
Robinson, LJ ;
Zaidi, M .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2005, 328 (03) :728-738
[8]   OSTEOARTHRITIS OF THE HIP AND OSTEOPOROSIS OF THE PROXIMAL FEMUR [J].
COOPER, C ;
COOK, PL ;
OSMOND, C ;
FISHER, L ;
CAWLEY, MID .
ANNALS OF THE RHEUMATIC DISEASES, 1991, 50 (08) :540-542
[9]   Proteinases in bone resorption:: obvious and less obvious roles [J].
Delaissé, JM ;
Engsig, MT ;
Everts, V ;
Ovejero, MD ;
Ferreras, M ;
Lund, L ;
Vu, TH ;
Werb, Z ;
Winding, B ;
Lochter, A ;
Karsdal, MA ;
Troen, T ;
Kirkegaard, T ;
Lenhard, T ;
Heegaard, AM ;
Neff, L ;
Baron, R ;
Foged, NT .
CLINICA CHIMICA ACTA, 2000, 291 (02) :223-234
[10]   Cathepsin K, but not cathepsins B, L, or S, is abundantly expressed in human osteoclasts [J].
Drake, FH ;
Dodds, RA ;
James, IE ;
Connor, JR ;
Debouck, C ;
Richardson, S ;
LeeRykaczewski, E ;
Coleman, L ;
Rieman, D ;
Barthlow, R ;
Hastings, G ;
Gowen, M .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (21) :12511-12516