Abstract

This study investigated the effects of advanced glycation end products (AGEs) on expressions of extracellular matrix metalloproteinase inducer (EMMPRIN) and matrix metalloproteinase-2 (MMP-2) in mouse osteoblasts. MC3T3-E1 cells were incubated with AGEs of different concentrations (50, 100, 200 and 400 mg/L) for various durations (12, 24 and 48 h). The expressions of EMMPRIN mRNA and protein as well as MMP-2 expression and activity were detected. Cells were treated with aminoguanidine (AG) of 0, 100, 200 and 400 µmol/L) plus 200 mg/L AGEs for 24 h, then expressions of EMMPRIN mRNA and protein were measured. Cells were treated with EMMPRIN antibody (5 μg/ml), and MMP-2 activity was determined with zymography. After AGEs treatment, the expressions of EMMPRIN mRNA and protein as well as MMP-2 expression and activity were significantly increased in a time and concentration dependent manner; AGEs plus AG of different concentrations could markedly decrease the expressions of EMMPRIN mRNA and protein when compared with controls in a concentration dependent manner; administration of EMMPRIN antibody dramatically suppressed the activity of MMP-2. AGEs could increase the expressions of EMMPRIN and MMP-2 and elevate MMP-2 activity; AG could suppress the increased expression of EMMPRIN induced by AGEs; EMMPRIN antibody conferred suppressive effects on the expression of MMP-2 induced by AGEs. Therefore, AGEs may be involved in the pathogenesis of osteoporosis via increasing the expression of EMMPRIN and MMP-2 and promoting MMP-2 activity. 

Key words: Advanced glycation end products, osteoblast, extracellular matrix metalloproteinase inducer, matrix metalloproteinase -2, osteoporosis.