Abstract
Estrogen plays an important role in maintaining normal bone metabolism via the direct or indirect regulation of bone cells. Osteoblastic cells, as the target cells of estrogen, can secrete multiple matrix metalloproteinases (MMPs) that participate in bone remodeling. It has been demonstrated that bone loss induced by estrogen deficiency is closely related to the abnormal expression of multiple MMPs in osteoblastic cells. However, the regulating action of estrogen on the expression of interstitial collagenases MMP-8 and MMP-13 in osteoblastic cells in vivo remains unclear. We used an ovariectomized osteoporotic rat model to analyze the changes in the histomorphometric parameters of bone after and without treatment with 17β-estradiol (E2); We also used immunohistochemistry and in situ hybridization to observe changes in the expression of mRNA and the proteins MMP-8, MMP-13 and TIMP-1 in osteoblastic cells in rat proximal tibia. In this study, we found that in the ovariectomized rat the expression of MMP-13 mRNA and protein increased markedly, whereas the expression of MMP-8 and TIMP-1 mRNA and protein did not change significantly. Our analysis showed that the expression of MMP-13 protein was correlated positively to bone trabecular separation, osteoid surface area, and negatively to trabecular numbers and the percentage of trabecula bone volume/total tissue volume. Our results suggest that MMP-13 plays an important role in estrogen deficiency-induced bone loss, while estrogen can inhibit bone resorption and reduce bone turnover rate by down-regulating the expression of MMP-13 in osteoblastic cells.
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References
DA Barondess M Singh SL Hendrix DAR Nelson (2002) ArticleTitleRadiographic measurements, bone mineral density, and the Singh Index in the proximal femur of white and black postmenopausal women Dis Mon 48 637–646
B Bodey B Bodey SuffixJr SE Siegel HE Kaiser (2000) ArticleTitleMatrix metalloproteinase expression in childhood medulloblastomas/primitive neuroectodermal tumors In Vivo 14 667–673
JJ Breckon S Papaioannou LW Kon A Tumber RM Hembry G Murphy JJ Reynolds MC Meikle (1999) ArticleTitleStromelysin (MMP-3) synthesis is up-regulated in estrogen-deficient mouse osteoblasts in vivo and in vitro J Bone Miner Res 14 1880–1890
RY Chen KL Wong JW Lawton FC Ho (1992) ArticleTitleAntinuclear antibody detection using streptavidin-biotin-peroxidase complex on HEp-2 cell substrate Asian Pac J Allergy Immunol 10 19–24
AM Delany JJ Jeffrey S Rydziel E Canalis (1995) ArticleTitleCortisol increases interstitial collagenase expression in osteoblasts by post-transcriptional mechanisms J Biol Chem 270 26607–26612
H Dobnig RT Turner (1995) ArticleTitleEvidence that intermittent treatment with parathyroid hormone increases bone formation in adult rats by activation of bone lining cells Endocrinology 136 3632–3638
RG Erben (1997) ArticleTitleEmbedding of bone samples in methylmethacrylate: an improved method suitable for bone histomorphometry, histochemistry, and immunohistochemistry J Histochem Cytochem 45 307–313
LM Golub NS Ramamurthy A Llavaneras ME Ryan HM Lee Y Liu S Bain T Sorsa (1999) ArticleTitleA chemically modified nonantimicrobial tetracycline (CMT-8) inhibits gingival matrix metalloproteinases, periodontal breakdown, and extra-oral bone loss in ovariectomized rats Ann NY Acad Sci 878 290–310
HE Gruber (1992) ArticleTitleAdaptations of Goldner’s Masson trichrome stain for the study of undecalcified plastic embedded bone Biotech Histochem 67 30–34
LS Holliday HG Welgus CJ Fliszar GM Veith JJ Jeffrey SL Gluck (1997) ArticleTitleInitiation of osteoclast bone resorption by interstitial collagenase J Biol Chem 272 22053–22058
W Hui AD Rowan T Cawston (2001) ArticleTitleInsulin-like growth factor 1 blocks collagen release and down regulates matrix metalloproteinase-1, -3, -8, and -13 mRNA expression in bovine nasal cartilage stimulated with oncostatin M in combination with interleukin 1alpha Ann Rheum Dis 60 254–261
PR Hurst RD Palmay (1999) ArticleTitleMatrix metalloproteinases and their endogenous inhibitors during the implantation period in the rat uterus Reprod Fertil Dev 11 395–402
SM Krane (1995) ArticleTitleIs collagenase (matrix metalloproteinase-1) necessary for bone and other connective tissue remodeling? Clin Orthop 313 47–53
MC Langub MC Monier-faugere Q Qi (2001) ArticleTitleParathyroid hormone/parathroid hormone-related peptide type 1 receptor in human bone J Bone Miner Res 16 448–456
JP Levine (2003) ArticleTitleLong-term estrogen and hormone replacement therapy for the prevention and treatment of osteoporosis Curr Womens Health Rep 3 181–186
EY Liao XH Luo (2001) ArticleTitleEffects of 17beta-estradiol on the expression of matrix metalloproteinase-1, -2 and tissue inhibitor of metalloproteinase-1 in human osteoblast-like cell cultures Endocrine 15 291–295
SK Lin SH Kok MY Kuo (2003) ArticleTitleoxide promotes infectious bone resorption by enhancingcytokine-stimulated interstitial collagenase synthesis in osteoblasts J Bone Miner Res 18 39–46
XH Luo EY Liao (2001) ArticleTitleProgesterone differentially regulates the membrane-type matrix metalloproteinase-1 (MT1-MMP) compartment of proMMP-2 activation in MG-63 cells Horm Metab Res 33 383–388
J Ma U Kitti O Teronen T Sorsa V Husa P Laine H Ronka T Salo C Lindqvist YT Konttinen (2000) ArticleTitleCollagenases in different categories of peri-implant vertical bone loss J Dent Res 79 1870–1873
D Massi A Franchi S Ketabchi M Paglierani N Pimpinelli M Santucci (2003) ArticleTitleExpression and prognostic significance of matrix metalloproteinases and their tissue inhibitors in primary neuroendocrine carcinoma of the skin Hum Pathol 34 80–88
P McClelland JE Onyia RR Miles Y Tu J Liang AK Harvey S Chandrasekhar JM Hock JP Bidwell (1998) ArticleTitleIntermittent administration of parathyroid hormone (1-34) stimulates matrix metalloproteinase-9 (MMP-9) expression in rat long bone J Cell Biochem 70 391–401
KV Menon P Angulo GM Boe KD Lindor (2003) ArticleTitleSafety and efficacy of estrogen therapy in preventing bone loss in primary biliary cirrhosis Am J Gastroenterol 98 889–892
A Mizutani I Sugiyama E Kuno (2001) ArticleTitleExpression of matrix metalloproteinases during ascorbate-induced differentiation of osteoblastic MC3T3-E1 cells J Bone Miner Res 16 2043–2049
M Notelovitz (2002) ArticleTitleWhy individualizing hormone therapy is crucial: putting the results of the WHI trial into perspective Medscape Womens Health 7 9
Y Okada (2000) ArticleTitleTumor cell–matrix interaction: pericellular matrix degradation and metastasis Verh Dtsch Ges Pathol 84 33–42
FS Panagakos S Kumar (1994) ArticleTitleModulation of proteases and their inhibitors in immortal human osteoblast-like cells by tumor necrosis factor-alpha in vitro Inflammation 18 243–265
AM Parfitt MK Drezner FH Glorieux (1987) ArticleTitleBone histomorphometry: standardization of omenclature, symbols and units J Bone Miner Res 2 595–610
ST Pattison J Melrose P Ghosh TK Taylor (2001) ArticleTitleRegulation of gelatinase-A (MMP-2) production by ovine intervertebral disc nucleus pulposus cells grown in alginate bead culture by Transforming Growth Factor-beta(1) and insulin like growth factor-I Cell Biol Int 25 679–689
C Pustovrh A Jawerbaum D Sinner M Pesaresi M Baier P Micone M Gimeno ET Gonzalez (2000) ArticleTitleMembrane-type matrix metalloproteinase-9 activity in placental tissue from patients with pre-existing and gestational diabetes mellitus Reprod Fertil Dev 12 269–275
Y Sasano JX Zhu M Tsubota (2002) ArticleTitleGene expression of MMP8 and MMP13 during embryonic development of bone and cartilage in the rat mandible and hind limb J Histochem Cytochem 50 325–332
M Tsuzaki G Guyton W Garrett (2003) ArticleTitleIL-1 beta induces COX2, MMP-1, -3 and -13, ADAMTS-4, IL-1 beta and IL-6 in human tendon cells J Orthop Res 21 256–264
M Uchida H Yamato Y Nagai (2001) ArticleTitleParathyroid hormone increases the expressionlevel of matrix metalloproteinase-13 in vivo J Bone Miner Metab 19 207–212
H Uusitalo A Hiltunen M Soderstrom HT Aro E Vuorio (2000) ArticleTitleExpression of cathepsins B, H, K, L, and S and matrix metalloproteinases 9 and 13 during chondrocyte hypertrophy and endochondral ossification in mouse fracture callus Calcif Tissue Int 67 382–390
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Li, J., Liao, EY., Dai, RC. et al. Effects of 17 β-estradiol on the expression of interstitial collagenases-8 and −13 (MMP-8 and MMP-13) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in ovariectomized rat osteoblastic cells. J Mol Hist 35, 723–731 (2004). https://doi.org/10.1007/s10735-004-6206-3
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DOI: https://doi.org/10.1007/s10735-004-6206-3