The nucleocytoplasmic shuttling protein CIZ reduces adult bone mass by inhibiting bone morphogenetic protein-induced bone formation

Mikihiko Morinobu, Tetsuya Nakamoto, Kazunori Hino, Kunikazu Tsuji, Zhong Jian Shen, Kazuhisa Nakashima, Akira Nifuji, Haruyasu Yamamoto, Hisamaru Hirai, Masaki Noda

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

Osteoporosis is a major health problem; however, the mechanisms regulating adult bone mass are poorly understood. Cas-interacting zinc finger protein (CIZ) is a nucleocytoplasmic shuttling protein that localizes at cell adhesion plaques that form where osteoblasts attach to substrate. To investigate the potential role of CIZ in regulating adult bone mass, we examined the bones in CIZ-deficient mice. Bone volume was increased and the rates of bone formation were increased in CIZ-deficient mice, whereas bone resorption was not altered. CIZ deficiency enhanced the levels of mRNA expression of genes encoding proteins related to osteoblastic phenotypes, such as alkaline phosphatase (ALP) as well as osterix mRNA expression in whole long bones. Bone marrow cells obtained from the femora of CIZ-deficient mice revealed higher ALP activity in culture and formed more mineralized nodules than wild-type cells. CIZ deficiency enhanced bone morphogenetic protein (BMP)-induced osteoblastic differentiation in bone marrow cells in cultures, indicating that BMP is the target of CIZ action. CIZ deficiency increased newly formed bone mass after femoral bone marrow ablation in vivo. Finally, BMP-2-induced bone formation on adult mouse calvariae in vivo was enhanced by CIZ deficiency. These results establish that CIZ suppresses the levels of adult bone mass through inhibition of BMP-induced activation of osteoblasts.

Original languageEnglish (US)
Pages (from-to)961-970
Number of pages10
JournalJournal of Experimental Medicine
Volume201
Issue number6
DOIs
StatePublished - Mar 21 2005

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Bone Morphogenetic Proteins
Osteogenesis
Bone and Bones
Proteins
Osteoblasts
Bone Marrow Cells
Alkaline Phosphatase
Bone Morphogenetic Protein 2
Messenger RNA
Focal Adhesions
Zinc Fingers
Bone Resorption
Thigh
Skull
Cell Adhesion
Femur
Osteoporosis
Cell Culture Techniques
Bone Marrow
Phenotype

ASJC Scopus subject areas

  • Immunology

Cite this

The nucleocytoplasmic shuttling protein CIZ reduces adult bone mass by inhibiting bone morphogenetic protein-induced bone formation. / Morinobu, Mikihiko; Nakamoto, Tetsuya; Hino, Kazunori; Tsuji, Kunikazu; Shen, Zhong Jian; Nakashima, Kazuhisa; Nifuji, Akira; Yamamoto, Haruyasu; Hirai, Hisamaru; Noda, Masaki.

In: Journal of Experimental Medicine, Vol. 201, No. 6, 21.03.2005, p. 961-970.

Research output: Contribution to journalArticle

Morinobu, M, Nakamoto, T, Hino, K, Tsuji, K, Shen, ZJ, Nakashima, K, Nifuji, A, Yamamoto, H, Hirai, H & Noda, M 2005, 'The nucleocytoplasmic shuttling protein CIZ reduces adult bone mass by inhibiting bone morphogenetic protein-induced bone formation', Journal of Experimental Medicine, vol. 201, no. 6, pp. 961-970. https://doi.org/10.1084/jem.20041097
Morinobu, Mikihiko ; Nakamoto, Tetsuya ; Hino, Kazunori ; Tsuji, Kunikazu ; Shen, Zhong Jian ; Nakashima, Kazuhisa ; Nifuji, Akira ; Yamamoto, Haruyasu ; Hirai, Hisamaru ; Noda, Masaki. / The nucleocytoplasmic shuttling protein CIZ reduces adult bone mass by inhibiting bone morphogenetic protein-induced bone formation. In: Journal of Experimental Medicine. 2005 ; Vol. 201, No. 6. pp. 961-970.
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