title: Possible involvement of the p57(Kip2) gene in bone metabolism.
abstract: We previously uncovered that growth stimulation of rat primary osteoblasts by transforming growth factor-beta1 (TGF-beta1) resulted in a dramatic decrease in p57(Kip2), a member of cyclin-dependent kinase (CDK) inhibitors, through the proteasomal degradation pathway (Urano et al., J. Biol. Chem. 274, 12197-12200, 1999). Here we demonstrated that the amount of p57 protein increases markedly, when rat calvarial primary osteoblasts treated with 1,25-dihydroxyvitamin D3 transit from proliferation toward differentiation. Next, we have analyzed the association of four amino acids deletion polymorphism of p57 and bone mineral density (BMD). The p57 genotype was determined in 154 postmenopausal Japanese women. When we separated the subjects into two groups, one having one or two copies of deletion polymorphism and the other without the deletion, the former subjects had higher BMD (Z score of total body, 0.67 +/- 0.93 vs 0. 23 +/- 0.90, mean +/- standard deviation; P = 0.021). Taken together, these findings suggest that the p57 regulated in the osteoblast proliferation and differentiation may play a role in determination of bone mineral density and pathogenesis of osteoporosis.
authors.affiliation: Department of Geriatric Medicine, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Urano
authors.forename: T
authors.initials: T
authors.lastname: Hosoi
authors.forename: M
authors.initials: M
authors.lastname: Shiraki
authors.forename: H
authors.initials: H
authors.lastname: Toyoshima
authors.forename: Y
authors.initials: Y
authors.lastname: Ouchi
authors.forename: S
authors.initials: S
authors.lastname: Inoue
mesh_terms: D000368:Aged; D000818:Animals; D001842:Bone and Bones / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D050761:Cyclin-Dependent Kinase Inhibitor p57; D005260:Female; D006801:Humans; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics*; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism; D011110:Polymorphism, Genetic; D017698:Postmenopause; D051381:Rats; D017207:Rats, Sprague-Dawley; D014807:Vitamin D / Q000494:pharmacology
chemical_list: C493964:CDKN1C protein, human; D050761:Cyclin-Dependent Kinase Inhibitor p57; D009687:Nuclear Proteins; D014807:Vitamin D