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- Title
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.
- Authors
Yun Jong Lee; Eun Bong Lee; Young Ee Kwon; Jung Jin Lee; Woo Shin Cho; Kim, Hyun A.; Yeong Wook Song
- 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 17β-estradiol, with or without 10–1,000 pg/mL of either interleukin (IL)-1β or tumor necrosis factor alpha (TNFα). 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 17β-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 TNFα, 17β-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-1β or TNFα above 10 pg/mL stimulation, 17β-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). 17β-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.
- Subjects
OSTEOARTHRITIS; ESTROGEN; METALLOPROTEINASES; CARTILAGE cells; METALLOENZYMES; PROTEINASES
- Publication
Rheumatology International, 2003, Vol 23, Issue 6, p282
- ISSN
0172-8172
- Publication type
Article
- DOI
10.1007/s00296-003-0312-5