2003 Fiscal Year Final Research Report Summary
Analysis of signal transduction and role of intracellular calcium in proliferation and differentiation of chondrocytes
| Project/Area Number |
12470309
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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 | HIROSHIMA UNIVERSITY (2002-2003)
Shimane Medical University (2000-2001) |
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Principal Investigator |
OCHI Mitsuo Hiroshima University, Graduate School of Biomedical Sciences, Professor, 大学院・医歯薬学総合研究科, 教授 (70177244)
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| Co-Investigator(Kenkyū-buntansha) |
ENOMOTO Koich Shimane University, School of Medicine, Research Associate, 医学部, 助手 (70112125)
MOCHIZUKI Yu Hiroshima University, Graduate School of Biomedical Sciences, Research Associate, 大学院・医歯薬学総合研究科, 助手 (10284192)
YASUNAGA Yuji Hiroshima University, Graduate School of Biomedical Sciences, Associate professor, 大学院・医歯薬学総合研究科, 助教授 (40253075)
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| Project Period (FY) |
2000 – 2003
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| Keywords | cartilage / c-fos / fetus / wound healing / intracellular calcium / ATP |
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| Research Abstract |
To compare the potential of adult and fetal animals to repair articular cartilage, we investigated the early process after creating superficial defects in the femoral knee cartilage using rat models. In fetuses at 19 days of gestation, both chondrocytes and the extracellular matrix responded remarkably by 48 hours after artificial injury of superficial defect. Staining patterns with safranin O revealed that by 1 hour after injury, some components of the extracellular matrix around the wound were modified, and the change spread from the limited region to the entire knee cartilage in 24 hours. The chondrocytes in the area surrounding the wound transiently expressed increased level of c fos from 1 to 6 hours. The wound remained 1 day after birth, i.e., 72 hours after injury, but was completely repaired 10 days after birth. In contrast, neither visible responses nor transient c fos expression was observed in 12-week-old adult articular cartilage 48 hours after injury. Then, we examined the relationships between intracellular Ca^<2+> concentration ([Ca^<2+>]_i and the induction of c-fos expression in the cartilage. Applications of ATP or Ca^<2+> ionophore A23187 that increase [Ca^<2+>]_i induced immediate expression of c-fos in primary cultured chondrocytes. One μM ATP elicited the increase of [Ca^<2+>]_i in chondrocytes in fetal but 1 mM was required in adult cartilage slices. Our findings showed that there is a signaling pathway, apparently active in the repair of fetal but not adult articular cartilage, that involves intercellular transfer of ATP, increase of [Ca^<2+>]_i, and expression of c-fos in the cartilage.
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