Novel function of CCN3: A regulator of endochondral ossification
Project/Area Number |
25462888
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Functional basic dentistry
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Research Institution | Okayama University |
Principal Investigator |
Hattori Takako 岡山大学, 医歯(薬)学総合研究科, 助教 (00228488)
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Co-Investigator(Kenkyū-buntansha) |
KUBOTA Satoshi 岡山大学, 大学院医歯薬学総合研究科, 教授 (90221936)
NISHIDA Takashi 岡山大学, 大学院医歯薬学総合研究科, 准教授 (30322233)
TAKIGAWA Masahasu 岡山大学, 大学院医歯薬学総合研究科, 教授 (20112063)
AOYAMA Eriko 岡山大学, 大学院医歯薬学総合研究科, 助教 (10432650)
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Project Period (FY) |
2013-04-01 – 2016-03-31
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Project Status |
Completed (Fiscal Year 2015)
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Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2013: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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Keywords | NOV/CCN3 / トランスジェニックマウス / 内軟骨性骨形成 / in situ hybridization / 間葉系細胞 / 軟骨分化 / 高密度培養系 / SFRP5 / 関節変性 / 血管侵入 / Col2a1 promoter |
Outline of Final Research Achievements |
To understand a role of CCN3 in bone formation, we generated a transgenic mouse line which is specifically overexpressing CCN3 in cartilage. The mice showed embryonic bone malformations, including shortened long bones, decreased bone mineralization, and delayed appearance of osteoblasts and cells expressing marker genes of late hypertrophy. Blood vessel invasion into the developing cartilage was also inhibited. In contrast, limb mesenchymal cells showed accelerated chondrogenesis. These phenomena correlated with changes in gene expression related to bone and cartilage development. Moreover, we observed degradation of articular chondrocytes and absorption of subchondral bone in adult knee joints. These findings demonstrate a novel role of CCN3 in skeletal development and maintenance of articular cartilage.
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Report
(4 results)
Research Products
(72 results)
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[Journal Article] Role of CCN2 in amino acid metabolism of chondrocytes2016
Author(s)
Murase, Y,, Hattori, T., Aoyama, E., Nishida, T., Maeda-Uematsu, A., Kawaki, H., Lyons, K. M., Sasaki, A., Takigawa, M., Kubota, S
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Journal Title
J. Cell Biochem
Volume: 117
Issue: 4
Pages: 927-937
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] CCN2 as a novel molecule supporting energy metabolism of chondrocytes.2014
Author(s)
Maeda-Uematsu A, Kubota S, Kawaki H, Kawata K, Miyake Y, Hattori T, Nishida T, Moritani N, Lyons KM, Iida S, Takigawa M.
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Journal Title
J Cell Biochem
Volume: 115
Issue: 5
Pages: 854-865
DOI
NAID
Related Report
Peer Reviewed / Open Access
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[Journal Article] Novel chondrogenic and chondroprotective effects of the natural compound harmine.2013
Author(s)
Hara, E. S., Ono, M., Kubota, S., Sonoyama, W., Oida, Y., Hattori, T., Nishida, T., Furumatsu, T., Ozaki, T., Takigawa, M. and Kuboki, T
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Journal Title
Biochimie
Volume: 95
Issue: 2
Pages: 347-381
DOI
Related Report
Peer Reviewed
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[Journal Article] Anti-fibrotic effect of CCN3 accompanied by altered gene expression profile of the CCN family.2013
Author(s)
Abd El Kader, T., Kubota, S., Janune, D., Nishida, T., Hattori, T., Aoyama, E., Perbal, B., Kuboki, T. and Takigawa, M.
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Journal Title
J. Cell Commun. Signal.
Volume: 7
Issue: 1
Pages: 11-18
DOI
Related Report
Peer Reviewed
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[Journal Article] Cartilage–specific overexpression of CCN family member 2/connective tissue growth factor (CCN2/CTGF) stimulates insulin-like growth factor expression and bone growth2013
Author(s)
Tomita, N., Hattori, T., Ito, S., Aoyama, E., Yao, M., Yamashiro, T., Takigawa M.
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Journal Title
PLoS One
Volume: 8
Issue: 3
Pages: e59226-e59226
DOI
NAID
Related Report
Peer Reviewed
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[Journal Article] CCN family member 2/connective tissue growth factor (CCN2/CTGF) has anti-aging effects that protect articular cartilage from age-related degenerative changes2013
Author(s)
Itoh, S., Hattori, T., Tomita, N., Aoyama, E., Yutani,Y., Yamashiro, T., Takigawa, M.
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Journal Title
PLoS One
Volume: 8
Issue: 8
Pages: e71156-e71156
DOI
NAID
Related Report
Peer Reviewed
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[Presentation] Metabolic impacts of CCN2 in chondrocytes.2015
Author(s)
Kubota, S., Murase, Y., Maeda-Uematsu, A., Hattori, T., Aoyama, E., Nishida, T., Kawaki, H., Lyons, K. M., Takigawa, M.
Organizer
Eight International Workishop on the CCN Family of Genes
Place of Presentation
Nice, France
Year and Date
2015-11-03
Related Report
Int'l Joint Research
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[Presentation] Role of interaction between CCN2 and Rab14 in vesicle trafficking in chondrocytes novel intracellular function of CCN2.2015
Author(s)
Hoshijima, M., Hattori, T., Aoyama, E., Nishida, T., Kubota, S., Kamioka, H., Takigawa, M.
Organizer
Eight International Workishop on the CCN Family of Genes
Place of Presentation
Nice, France
Year and Date
2015-11-03
Related Report
Int'l Joint Research
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[Presentation] Regenerative effects of CCN2 ondependent modules and CCN3 on articular chondrocytes/cartilage2015
Author(s)
Takigawa, M., Abd El Kader, T., Janune, D., Aoyama, E., Nishida, T., Hattori, T., Hara, E. S., One, M., Tabata, Y., Kuboki, T., Kubota, S.
Organizer
Eight International Workishop on the CCN Family of Genes
Place of Presentation
Nice, France
Year and Date
2015-11-03
Related Report
Int'l Joint Research
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[Presentation] Introducing CCN2 independent modules as a regenerative therapy for osteoarthritis and futher selecting the most suitable among them.2015
Author(s)
Abd El-Kader, T., Nishida, T., Hattori, T., Aoyama, E., Janune, D., Hara, E. S., Ono M., Tabata, Y., Kuboki, T., Kubota, S., Takigawa, M
Organizer
第7回日本CCNファミリー研究会若手国際学術奨励賞
Place of Presentation
岡山
Year and Date
2015-08-29
Related Report
Invited
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[Presentation] E6-AP/UBE3A Protein, a Ubiquitin Ligase toward SOX9 Protein is essential to endochondral ossification2015
Author(s)
Hattori, T., Kishino, T., Stephen, S., Eberspaecher, H., Maki, S., Takigawa, M., Nishida, T., Kubota, S., de Crombrugghe, B.and Yasuda, H.
Organizer
Gordon Research Conference, Cartilage Biology & Pathology
Place of Presentation
Hotel Galvez Galveston, TX.
Year and Date
2015-03-22 – 2015-03-27
Related Report
Invited
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[Presentation] Dual Origin of Endochondral Osteoblasts: A Novel Chondrocyte-derived Osteoprogenitor Cell Identified in Hypertrophic Cartilage near the Chondro-osseous Junction2015
Author(s)
von der Mark, K., Park J., Gebhardt, M., Surmann-Schmitt, C., Stock, M., Hattori, T., Hartmann, C., Zhou , X., and de Crombrugghe, B.
Organizer
Gordon Research Conference, Cartilage Biology & Pathology
Place of Presentation
Hotel Galvez Galveston, TX.
Year and Date
2015-03-22 – 2015-03-27
Related Report
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[Presentation] Assessment of the regenerative effects of CCN2 independent modules on chondrocytes in vitro and osteoarturiritis models in vivo.2014
Author(s)
Abd El Kdaer, T., Kubota, S., Nishida, T., Hattori, T., Aoyama, E., Janune, D., Hara, E. S., Ono, M., Tabata, Y., Kuboki, T., Takigawa, M.
Organizer
第37回日本分子生物学会
Place of Presentation
横浜
Year and Date
2014-11-25 – 2014-11-27
Related Report
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[Presentation] The regenerative effect of CCN2 independent modules on chondrocytes in vitro and osteoarturiritis models in vivo.2014
Author(s)
Abd El Kdaer, T., Kubota, S., Nishida, T., Hattori, T., Aoyama, E., Janune, D., Hara, E. S., Ono, M., Tabata, Y., Kuboki, T., Takigawa, M.
Organizer
第6回CCNファミリー研究会
Place of Presentation
岡山
Year and Date
2014-08-30
Related Report
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[Presentation] Crucial role of CCN2 in energy metabolism in chondrocytes.2013
Author(s)
Maeda, A., Kubota, S., Miyake, Y., Kawata, K., Hattori, T., Nishida, T., Moritani, N., Kawaki, H., Lyons, K., Iida, S., Takigawa, M.
Organizer
2nd joint meeting of IBMS-JSBMR
Place of Presentation
Kobe, Japan
Related Report
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[Presentation] Identification and characterization of chondrocytic fibroblast growth factor 1 as a molecular counterpart of CCN family member 2.2013
Author(s)
Abd El Kader, T., Kubota, S., Nishida, T., Hattori, T., Aoyama, E., Furumatsu, T., Kuboki, T., Takigawa, M.
Organizer
2nd joint meeting of IBMS-JSBMR
Place of Presentation
Kobe, Japan
Related Report
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[Presentation] Cartilage-specific overexpression of CCN3 negatively regulates endochondral bone formation.2013
Author(s)
Hattori, T., Ono, M., Hoshijima, M., Kadoya, K., Kuwahara, M., Oie, H., Miyake, Y., Kuboki, T., Takigawa, M.
Organizer
2nd joint meeting of IBMS-JSBMR
Place of Presentation
Kobe, Japan
Related Report
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[Presentation] Roles of CCN2 and CCN3 in skeletogenesis.2013
Author(s)
Masaharu Takigawa, Satoshi Kubota, Takako Hattori, Takashi Nishida, Eriko Aoyama, Nao Tomita, Shinsuke Ito, Danilo Janune, Mitsuhiro Hoshijima.
Organizer
The seventh International Workshop on the CCN Family of Genes
Place of Presentation
Nice, France
Related Report
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[Presentation] Anti-fibrotic role of CCN3 through regulation of CCN family genes2013
Author(s)
Abd El Kdaer, T., Kubota, S., Janune, D., Nishida, T., Hattori, T., Aoyama, E., Perbal, B., Takigawa, M.
Organizer
The third international symposium of medical-dental-pharmaceutical education and research in Okayama
Place of Presentation
岡山大学50周年記念会館
Related Report
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