title: Regulation of ER molecular chaperone prevents bone loss in a murine model for osteoporosis.
abstract: Endoplasmic reticulum (ER) stress response is important for protein maturation in the ER. Some murine models for bone diseases have provided significant insight into the possibility that pathogenesis of osteoporosis is related to ER stress response of osteoblasts. We examined a possible correlation between osteoporosis and ER stress response. Bone specimens from 8 osteoporosis patients and 8 disease-controls were used for immunohistochemical analysis. We found that ER molecular chaperones, such as BiP (immunoglobulin heavy-chain binding protein) and PDI (protein-disulfide isomerase) are down-regulated in osteoblasts from osteoporosis patients. Based on this result, we hypothesized that up-regulation of ER molecular chaperones in osteoblasts could restore decreased bone formation in osteoporosis. Therefore, we investigated whether treatment of murine model for osteoporosis with BIX (BiP inducer X), selective inducer BiP, could prevent bone loss. We found that oral administration of BIX effectively improves decline in bone formation through the activation of folding and secretion of bone matrix proteins. Considering these results together, BIX may be a potential therapeutic agent for the prevention of bone loss in osteoporosis patients.
authors.affiliation: Division of Molecular and Cellular Biology, Department of Anatomy, Faculty of Medicine, University of Miyazaki, Kihara 5200, Kiyotake, Miyazaki, 889-1692, Japan.
authors.forename: Shin-ichiro
authors.initials: S
authors.lastname: Hino
authors.forename: Shinichi
authors.initials: S
authors.lastname: Kondo
authors.forename: Kazuya
authors.initials: K
authors.lastname: Yoshinaga
authors.forename: Atsushi
authors.initials: A
authors.lastname: Saito
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Murakami
authors.forename: Soshi
authors.initials: S
authors.lastname: Kanemoto
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sekiya
authors.forename: Kazuyasu
authors.initials: K
authors.lastname: Chihara
authors.forename: Yuji
authors.initials: Y
authors.lastname: Aikawa
authors.forename: Hideaki
authors.initials: H
authors.lastname: Hara
authors.forename: Takashi
authors.initials: T
authors.lastname: Kudo
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Sekimoto
authors.forename: Taro
authors.initials: T
authors.lastname: Funamoto
authors.forename: Etsuo
authors.initials: E
authors.lastname: Chosa
authors.forename: Kazunori
authors.initials: K
authors.lastname: Imaizumi
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000831:Animals, Newborn; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001842:Bone and Bones / Q000187:drug effects / Q000473:pathology; D002478:Cells, Cultured; D004721:Endoplasmic Reticulum / Q000378:metabolism; D000091342:Endoplasmic Reticulum Chaperone BiP; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D008875:Middle Aged; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism*; D010006:Osteoblasts / Q000187:drug effects / Q000473:pathology; D053495:Osteopontin / Q000378:metabolism; D010024:Osteoporosis / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D019704:Protein Disulfide-Isomerases / Q000378:metabolism; D013861:Thiocyanates / Q000008:administration & dosage / Q000627:therapeutic use*; D013997:Time Factors
chemical_list: C527742:1-(3,4-dihydroxyphenyl)-2-thiocyanate-ethanone; D050071:Bone Density Conservation Agents; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D013861:Thiocyanates; D053495:Osteopontin; D019704:Protein Disulfide-Isomerases