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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

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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.

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Acknowledgements

We are grateful for the excellent technical help in real-time RT-PCR of M. Kinoshita Ph.D., Gene Diagnostic Center, Otsuka Assay Laboratories, Tokushima, Japan, and invaluable discussions on the results with K.A. Hasty Ph.D. and A.H. Kang MD Ph.D. of the University of Tennessee, USA.

This work was supported by a grant from the Korea Heath 21 R&D project, Ministry of Health and Welfare, Republic of Korea (HMP-00-C11–08–0007) and partially by the Basic Research Program of the Korea Science and Engineering Foundation, Korea (2000–215–001–3).

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Authors and Affiliations

  1. Department of Internal Medicine, Clinical Research Institute, Seoul National University College of Medicine, Seoul, Korea

    Yun Jong Lee, Eun Bong Lee, Young Ee Kwon, Jung Jin Lee, Hyun A. Kim & Yeong Wook Song

  2. Department of Orthopedic Surgery, College of Medicine, Ulsan University, Seoul, Korea

    Woo Shin Cho

  3. Department of Internal Medicine, Seoul National University Hospital, 28 Yongun-dong, Chongno-gu, 110–744, Seoul, Korea

    Yeong Wook Song

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  1. Yun Jong Lee
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Lee, Y.J., Lee, E.B., Kwon, Y.E. et al. 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. Rheumatol Int 23, 282–288 (2003). https://doi.org/10.1007/s00296-003-0312-5

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