2007 Fiscal Year Final Research Report Summary
Analysis of Wnt Signaling in Chondrogenic Differentiation for Osteoarthritis
| Project/Area Number |
18591655
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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 | The University of Tokyo |
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Principal Investigator |
MIURA Toshiki The University of Tokyo, Faculty of Medicine, Assistant Professor (20376479)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAYAMA Shuichi The University of Tokyo, Faculty of Medicine, Assistant Professor (80401066)
HARA Nobuhiro The University of Tokyo, Faculty of Medicine, Assistant Professor (00422296)
OGATA Naoshi The University of Tokyo, Faculty of Medicine, Visiting Assistant Professor (10361495)
KAWANO Hirotaka The University of Tokyo, Faculty of Medicine, Lecturer (20345218)
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| Project Period (FY) |
2006 – 2007
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| Keywords | Osteoarthritis / Canonical Wnt signaling / TCF / LEF-1 / Hypertrophy / Sox9 |
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| Research Abstract |
To better understand the role of the canonical Wnt signaling pathway in cartilage development and Osteoarthritis (OA) condition, we adenovirally expressed a constitutively active (ca) or a dominant negative (dn) form of lymphoid enhancer factor-1 (LEF-1), the main nuclear effecter of the pathway, in undifferentiated mesenchymal cells, chondrogenic cells and primary chondrocytes, and examined the expression of markers for chondrogenic differentiation and hypertrophy. caLEF-1 and LiCl, an activator of the canonical pathway, promoted both chondrogenic differentiation and hypertrophy, whereas dnLEF-1 and the gene silencing of β-catenin suppressed LiCl promoted effects. To investigate whether these effects were dependent on Sox9, a master regulator of cartilage development, we stimulated Sox9-deficient ES cells with the pathway. caLEF-1 and LiCl promoted both chondrogenic differentiation and hypertrophy in wild-type but not in Sox9-deficient cells. The response of Sox9-deficient cells was restored by the adenoviral expression of Sox9. Thus, the canonical Wnt signaling pathway promotes chondrocyte differentiation in a Sox9-dependent manner. Next, In vivo experiment, mouse OA model was created by surgical transection of the medial collateral ligament and resection of the medial meniscus of the knee joints of wild-type. Cartilage destruction and osteophyte formation in the medial tibial cartilage were compared by histologic and radiographic analyses. Expression of type X collagen, TCF/LEF-1 and β-catenin was examined by immunohistochemistry. TCF/LEF-1 was induced in the articular cartilage of wild-type mice at the early stage of OA, almost simultaneously with type X collagen as compared with wild-type mice. These in vivo results perform similar functions with that RUNX-2 contributes to the pathogenesis of OA through chondrocyte hypertrophy and matrixbreakdown after the induction of joint instability (Our group published).
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[Journal Article] Akt1 in osteoblasts and osteoclasts controls bone remodeling2007
Author(s)
Kawamura N, Kugimiya F, Oshima Y, Ohba S, Ikeda T, Saito T, Shinoda Y, Kawasaki Y, Ogata N, Hoshi K, Akiyama T, Tobe T, Kadowaki T, Azuma Y, Tanaka S, Nakamura K, Chung UI, and Kawaguchi H
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Journal Title
PLoS ONE 2(10)
Pages: e1058
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Carminerin contributes to chondrocyte calcification during endochondral ossification2006
Author(s)
Yamada T, Kawano H, Koshizuka Y, Fukuda T, Yoshimura K, Kamekura S, Saito T, Ikeda T, Kawasaki Y, Azuma Y, Ikegawa S, Hoshi K, Chung UI, Nakamura K, Kato S, Kawaguchi H
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Journal Title
Nat Med 12
Pages: 665-670
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Regulation of bone formation by adiponectin through autocrine/paracrine and endocrine pathways2006
Author(s)
Shinoda Y, Yamaguchi M, Ogata N, Akune T, Kubota N, Yamauchi T, Terauchi Y, Kadowaki T, Takeuchi Y, Fukumoto S, Ikeda T, Hoshi K, Chung UI, Nakamura K, Kawaguchi H.
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Journal Title
J Cell Biochem 99(1)
Pages: 196-208
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Runxl, co-activator of Sox5, Sox6 and Sox9(the Sox trio) regulates chondrogenic differentiation2007
Author(s)
Yano F, Ikeda T, Saito T, Ogata N, Takeda S, Kimura A, Ohba S, Kugimiya F, Nakamura K, Takato T, Kawaguchi H and Chung U.
Organizer
29th annual meeting of the American Society for Bone and Mineral Research
Place of Presentation
Honolulu, Hawaii, USA
Year and Date
20070916-20
Description
「研究成果報告書概要(欧文)」より
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