Membrane-type matrix metalloproteinase-1 (MT1-MMP) is down-regulated in estrogen-deficient rat osteoblast in vivo.
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.
Liao
E Y
EY
Institute of Endocrinology and Metabolism, The Second Xiangya Hospital of Central South University, Changsha, Hunan, PR China.
Liao
H J
HJ
Guo
L J
LJ
Zhou
H D
HD
Wu
X P
XP
Dai
R C
RC
Luo
X H
XH
D000818:Animals; D002478:Cells, Cultured; D015536:Down-Regulation; D004958:Estradiol / Q000502:physiology*; D005260:Female; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases / Q000235:genetics / Q000378:metabolism*; D010006:Osteoblasts / Q000201:enzymology*; D010024:Osteoporosis / Q000503:physiopathology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000235:genetics / Q000378:metabolism
D012333:RNA, Messenger; D019716:Tissue Inhibitor of Metalloproteinase-2; D004958:Estradiol; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2