title: Effect of selective estrogen receptor modulator/raloxifene analogue on proliferation and collagen metabolism of tendon fibroblast.
abstract: The selective estrogen receptor modulator raloxifene is therapeutically beneficial for postmenopausal connective tissue degradation, such as osteoporosis, vascular sclerosis, and dermal degradation; however, the effects of raloxifene on postmenopausal tendon metabolism have not been clarified. In this study, we investigated the effects of raloxifene analogue (LY117018) on cell proliferation and collagen metabolism using cultured rat Achilles tendon fibroblasts. 17beta-Estradiol (E(2); 10(-11)-10(-9) M) and LY117018 (10(-9)-10(-7) M) had no significant effects on tendon fibroblast proliferation, based on a BrdU (5-bromo-2'-deoxyuridine) incorporation assay (24 hr) and a WST-8 colorimetric assay (2 or 6 days). Neither E(2) nor LY117018 significantly altered the expression of type I collagen, which is a main component of the tendon extracellular matrix (ECM), whereas both E(2) and LY117018 significantly increased the expression of matrix metalloproteinase (MMP)-13, which is responsible for tendon collagen degradation in rat. Also, both E(2) and LY117018 increased the expression of type III collagen and elastin, which are minor components of tendon ECM, but are considered to govern the elastic properties of tendons. These changes in collagen and MMP induced by either E(2) or LY117018 were attenuated by the estrogen receptor alpha blocker ICI 182,780. The results of this study suggest that postmenopausal estrogen deficiency might downregulate tendon collagen turnover and decrease tendon elasticity. Further, raloxifene treatment might restore these changes to premenopausal levels.
authors.affiliation: Department of Orthopaedic Surgery, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Irie
authors.forename: Masahiko
authors.initials: M
authors.lastname: Takahata
authors.forename: Tokifumi
authors.initials: T
authors.lastname: Majima
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Abe
authors.forename: Miki
authors.initials: M
authors.lastname: Komatsu
authors.forename: Norimasa
authors.initials: N
authors.lastname: Iwasaki
authors.forename: Akio
authors.initials: A
authors.lastname: Minami
mesh_terms: D000125:Achilles Tendon / Q000166:cytology / Q000187:drug effects*; D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D024042:Collagen Type I / Q000378:metabolism; D024061:Collagen Type III / Q000378:metabolism; D004549:Elastin / Q000378:metabolism; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D000077267:Fulvestrant; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism; D011759:Pyrrolidines / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D020849:Raloxifene Hydrochloride / Q000031:analogs & derivatives*; D051381:Rats; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology*; D013778:Tetrazolium Salts / Q000378:metabolism; D013876:Thiophenes / Q000037:antagonists & inhibitors / Q000494:pharmacology*
chemical_list: C476329:2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H tetrazolium monosodium salt; D024042:Collagen Type I; D024061:Collagen Type III; D004965:Estrogen Antagonists; D011759:Pyrrolidines; D020845:Selective Estrogen Receptor Modulators; D013778:Tetrazolium Salts; D013876:Thiophenes; D000077267:Fulvestrant; D020849:Raloxifene Hydrochloride; D004958:Estradiol; C025430:LY 117018; D004549:Elastin; D053509:Matrix Metalloproteinase 13; D001973:Bromodeoxyuridine