2004 Fiscal Year Final Research Report Summary
Bone Marrow Cell Development and Signal Transduction in Bone Loss due to Skeletal Unloading.
| Project/Area Number |
14370475
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Orthopaedic surgery
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| Research Institution | University of Occupational and Environmental Health |
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Principal Investigator |
SAKAI Akinori University of Occupational and Environmental Health, School of Medicine, Associate Professor, 医学部, 助教授 (90248576)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAMURA Toshitaka University of Occupational and Environmental Health, School of Medicine, Professor, 医学部, 教授 (50082235)
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| Project Period (FY) |
2002 – 2004
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| Keywords | unloading / immobilization / trabecular bone / parathyroid hormone / osteblast / osteoclast / p53 / c-fos |
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| Research Abstract |
In 2002, our data showed that trabecular bone mass and bone formation were preserved after tail-suspension in p53(-/-) mice, closely associated with ALP-positive CFU-f and mineralized nodule formation in marrow cultures obtained from tibias of p53(-/-) mice. Bone loss due to mechanical unloading can be related to the facilitation of intracellular p53-p21 signaling. We also demonstrated that generation of nitric oxide through inducible nitric oxide synthase is essential for the stimulation of bone formation upon mechanical reloading.
In 2003, we clarified that skeletal unloading alleviated the anabolic action of intermittent parathyroid hormone (PTH) (1-34) in mouse tibia in association with inhibition of PTH-induced increase in c-fos mRNA in bone marrow cells. The PTH-induced increase in c-fos mRNA was depressed, but the increases in Osterix and RANKL mRNA were maintained. Unloading promoted the PTH-associated osteoclastogenesis and seemed to delay the progression of osteogenic differentiation in association with reduction of the PTH-dependent increase of c-fos mRNA in bone marrow cells.
In 2004, our data demonstrated that the decreased osteogenic potential after unloading was related to the reduction of PECAM-1 (CD31) expression in bone marrow cells, and that significant increases in osteoclast surface and number after skeletal unloading were suppressed in thyroparathyroidectomized mice, closely associated with the reduction in the high expression of RANKL mRNA in the tibial bone marrow cells.
Through these 3 years, we clarified that skeletal unloading reduced bone formation by the facilitation of intracellular p53-p21 signaling and the reduction of PECAM-1 expression in bone marrow cells, and that enhanced osteoclastogenesis due to skeletal unloading is related to the elevation of RANKL expression by the facilitation of parathyroid hormone signaling in bone marrow cells.
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Research Products
(9 results)
