title: Involvement of PRIP, phospholipase C-related, but catalytically inactive protein, in bone formation.
abstract: PRIP (phospholipase C-related, but catalytically inactive protein) is a novel protein isolated in this laboratory. PRIP-deficient mice showed increased serum gonadotropins, but decreased gonadal steroid hormones. This imbalance was similar to that for the cause of bone disease, such as osteoporosis. In the present study, therefore, we analyzed mutant mice with special reference to the bone property. We first performed three-dimensional analysis of the femur of female mice. The bone mineral density and trabecular bone volume were higher in mutant mice. We further performed histomorphometrical assay of bone formation parameters: bone formation rate, mineral apposition rate, osteoid thickness, and osteoblast number were up-regulated in the mutant, indicating that increased bone mass is caused by the enhancement of bone formation ability. We then cultured primary cells isolated from calvaria prepared from both genotypes. In mutant mice, osteoblast differentiation, as assessed by alkaline phosphatase activity and the expression of osteoblast differentiation marker genes, was enhanced. Moreover, we analyzed the phosphorylation of Smad1/5/8 in response to bone morphogenetic protein, with longer phosphorylation in the mutant. These results indicate that PRIP is implicated in the negative regulation of bone formation.
authors.affiliation: Laboratory of Molecular and Cellular Biochemistry, Kyushu University, Fukuoka 812-8582, Japan; Division of Fixed Prosthodontics, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Koshiro
authors.initials: K
authors.lastname: Tsutsumi
authors.affiliation: Laboratory of Molecular and Cellular Biochemistry, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Miho
authors.initials: M
authors.lastname: Matsuda
authors.affiliation: Laboratory of Molecular and Cellular Biochemistry, Kyushu University, Fukuoka 812-8582, Japan; Division of Orthodontics, Faculty of Dental Science, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Miho
authors.initials: M
authors.lastname: Kotani
authors.affiliation: Laboratory of Molecular and Cellular Biochemistry, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Mizokami
authors.affiliation: Division of Orthodontics, Faculty of Dental Science, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Ayako
authors.initials: A
authors.lastname: Murakami
authors.affiliation: Division of Orthodontics, Faculty of Dental Science, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Takahashi
authors.affiliation: Division of Fixed Prosthodontics, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Terada
authors.affiliation: Laboratory of Molecular and Cellular Biochemistry, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kanematsu
authors.affiliation: Laboratory of Genome and Biosignal, Tokyo University of Pharmacy and Life Science, Tokyo 192-0392, Japan.
authors.forename: Kiyoko
authors.initials: K
authors.lastname: Fukami
authors.affiliation: Division of Lipid Biochemistry, Graduate School of Medicine, Kobe University, Kobe 650-0017, Japan.
authors.forename: Tadaomi
authors.initials: T
authors.lastname: Takenawa
authors.affiliation: Department of Molecular Signaling and Biochemistry, Kyushu Dental College, Kitakyushu 803-8580, Japan.
authors.forename: Eijiro
authors.initials: E
authors.lastname: Jimi
authors.affiliation: Laboratory of Molecular and Cellular Biochemistry, Kyushu University, Fukuoka 812-8582, Japan. Electronic address: hirata1@dent.kyushu-u.ac.jp.
authors.forename: Masato
authors.initials: M
authors.lastname: Hirata
mesh_terms: D000818:Animals; D001842:Bone and Bones / Q000378:metabolism; D002384:Catalysis; D002454:Cell Differentiation; D005260:Female; D005269:Femur / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008954:Models, Biological; D056918:Nuclear Receptor Coactivators / Q000378:metabolism*; D010006:Osteoblasts / Q000166:cytology; D010010:Osteoclasts / Q000166:cytology; D010012:Osteogenesis / Q000502:physiology*; D010052:Ovariectomy; D010766:Phosphorylation; D051785:Smad Proteins / Q000378:metabolism; D014057:Tomography, X-Ray Computed / Q000379:methods; D010738:Type C Phospholipases / Q000378:metabolism*
chemical_list: C405683:Ncoa6 protein, mouse; D056918:Nuclear Receptor Coactivators; D051785:Smad Proteins; D010738:Type C Phospholipases