2011 Fiscal Year Final Research Report
Studies about the regulation of cartilage growth and differentiation by Gdf5, main regulator of joint formation in digits
| Project/Area Number |
21591955
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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 |
Orthopaedic surgery
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| Research Institution | Wakayama Medical University |
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Principal Investigator |
ITOH Shunji 和歌山県立医科大学, 医学部, 助教 (50275351)
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| Co-Investigator(Kenkyū-buntansha) |
MURAGAKI Yasuteru 和歌山県立医科大学, 医学部, 教授 (40190904)
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| Project Period (FY) |
2009 – 2011
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| Keywords | 関節病学 / アポトーシス |
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| Research Abstract |
Tricho-rhino-phalangeal syndrome (TRPS) is an autosomal dominant skeletal disorder caused by mutations of the TRPS1 gene. Althogh TRPS is characterized by deformed epiphysis of the digits, the pathological mechanism remain unknown. Our previous study showed that the Trps1 protein synthesis was regulated by Gdf5, an early marker of joint formation. In this study, we hypothesized that Trps1 has some roles in the Gdf5 signaling pathway that formed joints of the digits and examined the joint formation of the digits in the Trps1-dificient (KO) mice. We found that the joint formation was incomplete due to lack of the superficial layer of the articular cartilage in KO mice. To address which proteins are involved in the incompletely formed joints downstream of Gdf5/Trps1, we examined the expression of several proteins related to joint formation by RT-PCR. We found that Prg4, a major component of the synovial fluid, was reduced in KO mice. Prg4 was expressed in the superficial layer of the developing digits of wild type mice, whereas it was discontinuously expressed in KO mice. Using ATDC5 cells, a chondrogenic cell line, we revealed that Gdf5 induced Prg4 expression in ATDC5 cells and that Trps1 promoted the Prg4 induction by Gdf5. These data suggest that the Gdf5/Trps1 pathway may be involved in joint formation of the digits by inducing Prg4 expression in the superficial layer.
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