title: Interrelationship of circulating matrix metalloproteinase-9, TNF-α, and OPG/RANK/RANKL systems in COPD patients with osteoporosis.
abstract: Previous studies have shown that matrix metalloproteinase-9 (MMP-9) and its cognate inhibitor TIMP-1, inflammatory cytokine TNF-α, and the OPG/RANK/RANKL system may each play individual roles in the pathogenesis of osteoporosis in patients with COPD. In the present study, we investigated the interrelationships of these factors in male COPD patients with and without osteoporosis. The serum levels of MMP-9, MMP-9/TIMP-1 ratio, TNF-α, RANKL, OPG, and the RANKL/OPG ratio were higher in COPD patients with osteoporosis than in individuals with normal or low bone mineral density (BMD) (N = 30, all P < 0.05 or < 0.01). The lung function FEV1%Pre and the BMD of the lumbar spine and femoral neck were found to be negatively correlated with MMP-9 serum level (r = -0.36, P < 0.05, r = -0.58, P < 0.001, and r = -0.62, P < 0.01, respectively), RANKL serum level (r = -0.21, P < 0.05, and r = -0.25, P < 0.05, and r = -0.26, P < 0.05, respectively), and RANKL/OPG ratio (r = -0.23, P < 0.05, r = -0.33, P < 0.05, and r = -0.38, P < 0.05, respectively). However, they had no correlation with TIMP-1, TNF-α, OPG, or RANK. The MMP-9 serum level was found to be positively correlated with TNF-α level (r = 0.35, P < 0.05) and RANKL/OPG ratio (r = 0.27, P < 0.05) but not associated with RANKL. These results suggest that MMP-9, TNF-α, and the OPG/RANK/RANKL system may be closely interrelated and may play interactive roles in pathogenesis of osteoporosis in COPD.
authors.affiliation: 1Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University , Guangzhou 510515 , China.
authors.forename: Pei-fang
authors.initials: PF
authors.lastname: Zhang
authors.forename: Lei
authors.initials: L
authors.lastname: Pan
authors.forename: Zhi-yang
authors.initials: ZY
authors.lastname: Luo
authors.forename: Hai-jin
authors.initials: HJ
authors.lastname: Zhao
authors.forename: Shao-xi
authors.initials: SX
authors.lastname: Cai
mesh_terms: D000368:Aged; D015992:Body Mass Index; D015519:Bone Density; D016022:Case-Control Studies; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D008875:Middle Aged; D010024:Osteoporosis / Q000150:complications / Q000378:metabolism*; D053244:Osteoprotegerin / Q000378:metabolism*; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications / Q000378:metabolism*; D053245:RANK Ligand / Q000378:metabolism*; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000378:metabolism*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D019715:Tissue Inhibitor of Metalloproteinase-1; D014409:Tumor Necrosis Factor-alpha; D020780:Matrix Metalloproteinase 9