2003 Fiscal Year Final Research Report Summary
Molecular mechanism of osteogenesis-induced osteogenesis
| Project/Area Number |
14370591
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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 |
Functional basic dentistry
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| Research Institution | Niigata University |
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Principal Investigator |
KAWASHIMA Hiroyuki Niigata University, Graduate School of Medical and Dental Sciences, 大学院・医歯学総合研究科, 教授 (40169719)
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| Co-Investigator(Kenkyū-buntansha) |
IKEGAME Mika Niigata University, Graduate School of Medical and Dental Sciences, Assistant, 大学院・医歯学総合研究科, 助手 (70282986)
YOSHIZAWA Tatsuya Niigata University, Graduate School of Medical and Dental Sciences, Assistant, 大学院・医歯学総合研究科, 助手 (40313530)
ISHIBASHI Osamu Niigata University, Graduate School of Medical and Dental Sciences, Assistant, 大学院・医歯学総合研究科, 助手 (70293214)
MATSUDA Akio Niigata University, Graduate School of Medical and Dental Sciences, Assistant, 大学院・医歯学総合研究科, 助手 (10359705)
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| Project Period (FY) |
2002 – 2003
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| Keywords | Mechanical stress / Osteogenesis / Osteoblast differentiation / α-adaptin C / Periodontal ligament / Mineralization / Msx2 / OPLL |
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| Research Abstract |
We have recently demonstrated mechanical stress (MS)-induced osteoblast differentiation and subsequent osteogenesis in vitro, and suggested that BMP-4 may act as an autocrine/paracrine factor in this process. We have also identified more than 100 genes that are either up-or down-regulated by MS. Alpha-adaptin C is one such gene and is known to play a role in endocytosis as one of the constituents of coated pits/vesicles. In situ hybridization and immunohistochemical studies demonstrated that mRNA as well as protein of α-adaptin C was induced as early as 3 hr under MS loading. The expression overlapped with that of BMP-4, suggesting that these cells eventually differentiate into osteoblasts. Electron microscopy demonstrated that coated pits/vesicles increased in those areas where cells, under MS, become strongly positive with α-adaptin C. In addition, potassium depletion, a manipulation known to block endocytosis, inhibited MS-induced osteoblast differentiation. These data strongly sugg
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est that α-adaptin C is involved in the MS-induced osteoblast differentiation via stimulating endocytosis of molecules such as EGF receptors. To further characterize genes involved in MS-induced osteogenesis, we also compared gene expression between osteoblasts and periodontal ligament (PDL) cells. Our working hypothesis was that PDL cells may be equipped with a mechanism by which calcification is suppressed, since the PDL never calcifies in vivo despite esposure to strong intermittent MS and despite their reported osteogenic potential. Indeed, murine cell line PDL-L2 (recently established by us) does not produce mineralized nodules in vitro without superphysiological amounts of BMP-2. We showed that Msx2, one of the genes which are much more abundant in PDL-L2 than in osteoblasts, is a key regulator that prevents PDL-L2 cells from trans-differentiating into osteoblasts. We also demonstrated that Msx2 expression is suppressed in a symptom-dependent manner in affected ligaments of patients with OPLL. We further showed that Msx2 prevents PDL-L2 cells from mineralization by suppressing Runx2 action through directly binding to Runx2 and recruiting HDAC1 complex. We also demonstrated that MS failed to mineralize PDL-L2 cells in vitro, whereas it enhanced mineralization. of osteoblasts. Less
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Research Products
(6 results)
