Membrane-type matrix metalloproteinase-1 (MT1-MMP) is down-regulated in estrogen-deficient rat osteoblast in vivo

• Published in: Journal of endocrinological investigation Vol. 27; no. 1; pp. 1 - 5
• Main Authors: Liao, E Y, Liao, H J, Guo, L J, Zhou, H D, Wu, X P, Dai, R C, Luo, X H
• Format: Journal Article
• Language: English
• Published: Italy 01.01.2004
• Subjects: Animals; Cells, Cultured; Down-Regulation; Estradiol - physiology; Female; Immunohistochemistry; In Situ Hybridization; Matrix Metalloproteinase 2 - genetics; Matrix Metalloproteinase 2 - metabolism; Matrix Metalloproteinases, Membrane-Associated; Metalloendopeptidases - genetics; Metalloendopeptidases - metabolism; Osteoblasts - enzymology; Osteoporosis - physiopathology; Rats; Rats, Sprague-Dawley; RNA, Messenger - analysis; Tissue Inhibitor of Metalloproteinase-2 - genetics; Tissue Inhibitor of Metalloproteinase-2 - metabolism
• ISSN: 0391-4097; 1720-8386
• DOI: 10.1007/BF03350902

Our previous study showed that estrogen stimulates membrane-type matrix metalloproteinases-1 (MT1-MMP) production in osteoblastic cells culture, but has no effect on MMP-2 and TIMP-2 synthesis. Osteoblast-derived MT1-MMP have been recently implied to play a role in bone metabolism by degrading tumor necrosis factor-alpha (TNF-alpha), resolving extracellular matrix and activating proMMP-2, which requires the process of activation mediated by MT1-MMP/tissue inhibitor of metalloproteinase (TIMP-2) complex on the cell surface. To investigate the mechanism of bone loss following estrogen deficiency, we examined the effects of estrogen on osteoblast synthesis of MT1-MMP, MMP-2 and TIMP-2. In situ hybridization and immunohistochemistry of rat bone samples were used to document the synthesis of MT1-MMP, MMP-2, and TIMP-2 mRNA and protein. Osteoblasts from distal femoral head showed an increase in the pattern of MT1-MMP mRNA and protein production in sham-operated controls and 17beta-estradiol (E2)-treated rats, compared with the ovariectomized group; the synthesis of MMP-2 and TIMP-2 mRNA and protein was unaffected. Our data show a down-regulation of MT1-MMP synthesis by osteoblast in vivo following estrogen withdrawal, and treatment with E2 resulted in induced MT1-MMP expression in vivo. There is evidence suggesting a role for MT1-MMP in the process of bone loss during the pathogenesis of osteoporosis.