[Variance of expressions of extracellular matrix components and effects of anti-osteoporotic drugs on Mönckeberg's arteriosclerosis].
Mönckeberg-type arteriosclerosis occurs as a complication in diabetic, uremic patients and in postmenoposal women. It has been shown that arterial calcification generates loss of elasticity in tunica media. We have already reported that the expression of tropoelastin (TE), the precursor protein of elastin, is suppressed by arterial calcification, although no changes of mRNA expression of the other elastic fiber components, such as fibrillins, was observed. We examined the effects of bisphosphonates, known as anti-osteoporotic drugs, in inorganic phosphate (Pi)-induced calcified bovine aortic smooth muscle cells (BASMCs) (in vitro arterial calcification model). Treatment with the bisphosphonate risedronate, significantly inhibited calcium deposition in the arterial calcification model. Risedronate also inhibited suppression of TE mRNA expression and the progression of osteopontin (OPN) and core binding factor-alpha1 (Cbfa1), an osteogenic transcription factor, by BASMCs calcification. Basically, bisphosphonates could inhibit phenotypic transition such as SMC to osteoblast-like cell. Inhibitory effects of bisphosphonates were also shown in female Sprague-Dawley rats with calcinosis induced by administration of an over-dose of vitamin D2 (in vivo arterial calcification model). It is known that arterial calcification is accelerated by oxidative low-density lipoprotein (oxLDL). Therefore we examined the effects of 7-ketocholesterol (7kc), a component of oxLDL, on in vitro arterial calcification. Thereupon, it was revealed that 7kc drastically accelerated Pi-induced calcification, and risedronate completely restored the calcification and mRNA expression accelerated by 7kc.
Saitoh
Eiji
E
Department of Clinical Chemistry, Hoshi University School of Pharmacy and Pharmaceutical Sciences, Tokyo, Japan.
Nagae
Yoshiyuki
Y
Wachi
Hiroshi
H
Seyama
Yoshiyuki
Y
D000818:Animals; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D002417:Cattle; D012968:Etidronic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005109:Extracellular Matrix / Q000378:metabolism*; D005260:Female; D006801:Humans; D007653:Ketocholesterols; D008077:Lipoproteins, LDL; D050380:Monckeberg Medial Calcific Sclerosis / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000068296:Risedronic Acid; D014333:Tropoelastin / Q000378:metabolism*
D050071:Bone Density Conservation Agents; D007653:Ketocholesterols; D008077:Lipoproteins, LDL; D014333:Tropoelastin; C099252:oxidized low density lipoprotein; D000068296:Risedronic Acid; D012968:Etidronic Acid; C003001:7-ketocholesterol