Deficiency of CIZ, a nucleocytoplasmic shuttling protein, prevents unloading-induced bone loss through the enhancement of osteoblastic bone formation in vivo.
Disuse osteoporosis is a major cause to increase the risk of fractures in bed-ridden patients whose numbers are increasing in our modern society. However, the mechanisms underlying the sensing of mechanical stress in bone are largely unknown. CIZ localizes at cell adhesion plaque and transfers into nuclear compartments and activates promoters of the genes encoding enzymes, which degrade matrix proteins to link signals from the cell adhesion site to nuclear events. We examined whether this nucleocytoplasmic shuttling protein would be involved in mediation of mechanical stress signaling. Unloading based on tail suspension reduced bone volume in wild-type mice. In contrast, CIZ-deficient mice revealed suppression in such reduction of bone mass due to unloading. Histomorphometric analysis revealed that unloading suppressed the levels of osteoblastic bone formation parameters, and such suppression of bone formation parameters was blocked by CIZ-deficiency. Osteoclastic bone resorption parameters were similar regardless of CIZ-deficiency after 2-week unloading. Mineralized nodule formation in the cultures of bone marrow cells obtained from the bone of mice subjected to unloading was suppressed in wild-type mice. CIZ deficiency blocked such reduction in nodule formation induced by unloading. These data indicated that nucleocytoplasmic shuttling protein, CIZ, plays a pivotal role in the response of bone mass in unloading condition.
Hino
K
K
Department of Molecular Pharmacology, Tokyo Medical and Dental University, Tokyo, Japan.
Nakamoto
T
T
Nifuji
A
A
Morinobu
M
M
Yamamoto
H
H
Ezura
Y
Y
Noda
M
M
D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D019417:Hindlimb Suspension / Q000009:adverse effects; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D034521:Nuclear Matrix-Associated Proteins / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D029543:Nucleocytoplasmic Transport Proteins / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D010006:Osteoblasts / Q000473:pathology / Q000502:physiology; D010012:Osteogenesis; D010024:Osteoporosis / Q000000981:diagnostic imaging / Q000473:pathology / Q000517:prevention & control*; D011859:Radiography; D014157:Transcription Factors / Q000172:deficiency* / Q000235:genetics / Q000502:physiology
D034521:Nuclear Matrix-Associated Proteins; D029543:Nucleocytoplasmic Transport Proteins; D014157:Transcription Factors; C499081:Zfp384 protein, mouse