| Project/Area Number |
09671870
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Morphological basic dentistry
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| Research Institution | TOKYO DENTAL COLLEGE |
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Principal Investigator |
WATANABE Hiroki TOKYO DENTAL COLLEGE,DEPARTMENT OF DENTISTRY,LECTURER, 歯学部, 講師 (00158651)
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| Project Period (FY) |
1997 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1999: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1998: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1997: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Keywords | Cytoskeleton / mRNA / transport / sorting / osteoblast / osteopetrosis / culture cell / csf-1 / In situ hybridization |
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| Research Abstract |
Actin isoform sorting has been shown to occur in a variety of cell types in culture. To this list we add osteoblasts, in which we show by in situ hybridization that beta-actin is distributed primarily in cell process and on one side of the nucleus and gamma-actin has a perinuclear distribution. Osteoblasts from the skeletal mutation toothless(tl), evaruated under identical conditions, fail to sort these actin isoforms differentially and exhibit diffuse labeling as their major manifestation. Northan analyses of actin mRNAs showed no differences between normal and mutant cultures. Shortened osteoblast life span and an inability to direct osteoclast-mediated bone resorption have recently been demonstrated in tl mutants. The present results suggest that a failure of osteoblasts to sort actin mRNAs may be related to one or both of these pathological magnifestation in this mutation and represent, to our knowledge, the first correction of an actin mRNA-sorting abnormality with a mammalian disease. Because bone resorption and formation are highly interdependent and injections of CSF-1, a growth factor, we examined the effects of CSF-1 treatment on ability to sort actin mRNAs in vitro. Neonatal CSF-1 treatment of mutants restores osteoblasts on older bone surfaces, promotes normal sorting of beta-actin mRNA in mutant osteoblasts in vitro without normalizing gamma-actin distribution. These data suggest the beta and gamma-actin mRNAs in osteoblasts are sorted by different mechanisms and that the differential sorting of beta-actin mRNA is related to the characteristic polarization of stress fibers in osteoblasts. This experimental system can be used to explore the relationships and regulation of these aspects of cell and tissue biology.
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