Effect of estrogen on the expression of matrix metalloproteinase (MMP)-1, MMP-3, and MMP-13 and tissue inhibitor of metalloproternase-1 in osteoarthritis chondrocytes

Abstract

The aim of this study was to evaluate the effect of estrogen on matrix metalloproteinase (MMP)-1, MMP-3, MMP-13, and tissue inhibitor of metalloproteinase (TIMP)-1 in osteoarthritic chondrocytes. Chondrocytes from the knee cartilage of 25 postmenopausal osteoarthritic (OA) patients were cultured under various conditions: 0 pg/mL, 50 pg/mL, 500 pg/mL, and 5,000 pg/mL of 17beta-estradiol, with or without 10-1,000 pg/mL of either interleukin (IL)-1beta or tumor necrosis factor alpha (TNFalpha). MMP-1, MMP-3, MMP-13, and TIMP-1 in the conditioned media were analyzed with immunoblot or enzyme-linked immunosorbent assay (ELISA). Type II collagenolytic activity was measured by fluorogenic type II collagenolytic activity assay. Real-time reverse transcriptase polymerase chain reaction (RT-PCR) using SYBR Green I dye was performed for the quantification of mRNA. Without cytokine stimulation, the secretion of MMP-1 was significantly reduced by 50 pg/mL of 17beta-estradiol (in immunoblot by a median of 12.3%, P=0.007; in ELISA by a median of 18.4%, P=0.001), and 500 pg/mL (in immunoblot by a median of 23.1%, P=0.001; in ELISA by a median of 21.0%, P=0.001). Additionally, under 10 pg/mL TNFalpha, 17beta-estradiol also significantly suppressed the secretion of MMP-1 (in immunoblot by a median of 39.0%, P=0.016; in ELISA by a median of 38.4%, P=0.041). Estrogen did not exert any significant effect on MMP-3, MMP-13, or TIMP-1 expression. With IL-1beta or TNFalpha above 10 pg/mL stimulation, 17beta-estradiol demonstrated no effect on MMP-1, MMP-3, MMP-13, or TIMP-1 secretion. Type II collagenolytic activity in the 50 pg/mL estradiol group decreased by 9.6% (-51.5-5.5%, P>0.05). 17beta-estradiol showed a tendency to decrease in MMP-1 mRNA. Estrogen may improve the imbalance between the amounts of MMPs and TIMP in chondrocytes, and these results suggest that hormone replacement therapy may provide some chondroprotective effect.

17β-estradiol reduces expression of MMP-1, -3, and -13 in human primary articular chondrocytes from female patients cultured in a three dimensional alginate system

“…Besides other proteins, proteoglycans are the substrate of MMP-3 (Huppertz et al 1998). In contrast to our results, Lee et al (2003) did not find any significant effect of estrogens on MMP-3 expression on protein level using immunoblot. However, parallel to the findings reported here, increased MMP-3 mRNA in knee cartilage of ovariectomized rabbits could be suppressed by estrogen supplement .…”

Effects of ultrasound on estradiol level, bone mineral density, bone biomechanics and matrix metalloproteinase-13 expression in ovariectomized rabbits

“…It has previously been reported that 17β-estradiol promotes the synthesis of type II collagen, in addition to other proteins such as insulin in articular chondrocytes (47). Lee et al demonstrated that 17β-estradiol inhibits the expression of MMP-13 in chondrocytes (48). Lu et al reported that estrogen deficiency may result in increased expression of MMP-13 (49).…”

Myocardial Matrix Remodeling and the Matrix Metalloproteinases: Influence on Cardiac Form and Function

“…There is no direct evidence to date to suggest that a MMP promoter region contains a hormone response element (HRE) (389). Although it has been demonstrated that other steroids can modulate MMP expression, the effects of these steroids on the transcriptional regulation are likely due to indirect mechanisms of action (94,223 ET is another bioactive molecule that likely contributes to the adverse myocardial remodeling process. One intracellular event following ET receptor activation is to activate members of the protein kinase C (PKC) family.…”