Involvement of PRIP, phospholipase C-related, but catalytically inactive protein, in bone formation

Koshiro Tsutsumi, Miho Matsuda, Miho Kotani, Akiko Mizokami, Ayako Murakami, Ichiro Takahashi, Yoshihiro Terada, Takashi Kanematsu, Kiyoko Fukami, Tadaomi Takenawa, Eijiro Jimi, Masato Hirata

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)31032-31042
Number of pages11
JournalJournal of Biological Chemistry
Volume286
Issue number35
DOIs
Publication statusPublished - Sep 2 2011

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Type C Phospholipases
Osteogenesis
Bone
Osteoblasts
Proteins
Phosphorylation
Bone and Bones
Bone Morphogenetic Proteins
Bone Diseases
Differentiation Antigens
Gonadal Steroid Hormones
Gonadotropins
Minerals
Skull
Bone Density
Femur
Osteoporosis
Alkaline Phosphatase
Cultured Cells
Genotype

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Involvement of PRIP, phospholipase C-related, but catalytically inactive protein, in bone formation. / Tsutsumi, Koshiro; Matsuda, Miho; Kotani, Miho; Mizokami, Akiko; Murakami, Ayako; Takahashi, Ichiro; Terada, Yoshihiro; Kanematsu, Takashi; Fukami, Kiyoko; Takenawa, Tadaomi; Jimi, Eijiro; Hirata, Masato.

In: Journal of Biological Chemistry, Vol. 286, No. 35, 02.09.2011, p. 31032-31042.

Research output: Contribution to journalArticle

Tsutsumi, Koshiro ; Matsuda, Miho ; Kotani, Miho ; Mizokami, Akiko ; Murakami, Ayako ; Takahashi, Ichiro ; Terada, Yoshihiro ; Kanematsu, Takashi ; Fukami, Kiyoko ; Takenawa, Tadaomi ; Jimi, Eijiro ; Hirata, Masato. / Involvement of PRIP, phospholipase C-related, but catalytically inactive protein, in bone formation. In: Journal of Biological Chemistry. 2011 ; Vol. 286, No. 35. pp. 31032-31042.
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