Mechanism and expression of CD302 as a new regulator of osteoclast maturation

• Project/Area Number: 15K11038
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Functional basic dentistry
• Research Institution: Okayama University
• Principal Investigator: Aoyama Eriko 岡山大学, 医歯薬学総合研究科, 助教 (10432650)
• Co-Investigator(Kenkyū-buntansha): 滝川 正春 岡山大学, 医歯薬学総合研究科, 教授 (20112063) ; 服部 高子 岡山大学, 医歯薬学総合研究科, 助教 (00228488) ; 西田 崇 岡山大学, 医歯薬学総合研究科, 准教授 (30322233) ; 久保田 聡 岡山大学, 医歯薬学総合研究科, 教授 (90221936)
• Co-Investigator(Renkei-kenkyūsha): HOSHIJIMA Mitsuhiro 岡山大学, 医歯薬学総合研究科, 助教 (30736567)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 破骨細胞 / アクチンリング / CD302/DCL-1 / 骨吸収 / osteoclast / actin / actin ring / CCN2/CTGF / CCN 2/CTGF

Outline of Final Research Achievements

CD302/DCL-1 is one of the C-type lectin receptors, but the distribution and the function has been mostly not clarified. We found that CD302 was expressed on osteoclasts induced from murine bone marrow cells. The inhibition of CD302 expression caused fragmentation of actin ring in mature osteoclasts and reduced bone resorption in vitro. Also, CD302 was co-localized with CCN2 which is a positive regulator of osteoclast maturation. Moreover, SHP-2 was identified as a potent candidate as a signal transducer of CD302 signaling. These results showed that CD302 could be a new target protein to regulate osteoclast maturation.

Research Products

• [Journal Article] UPR Transducer BBF2H7 Allows Export of Type II Collagen in a Cargo- and Developmental Stage-Specific Manner (2017)
  • Author(s): Tokiro Ishikawa, Takuya Toyama, Yuki Nakamura, Kentaro Tamada, Hitomi Shimizu, Satoshi Ninagawa, Tetsuya Okada, Yasuhiro Kamei, Tomoko Ishikawa-Fujiwara, Takeshi Todo, Eriko Aoyama, Masaharu Takigawa, Akihiro Harada and Kazutoshi Mori
  • Journal Title: Journal of cell biology Volume: 印刷中 Issue: 6 Pages: 1761-1774
  • DOI: 10.1083/jcb.201609100
  • NAID: 120006343784
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] A tumor suppressor gene product, platelet-derived growth factor receptor-like protein controls chondrocyte proliferation and differentiation. (2017)
  • Author(s): Kawata K, Kubota S, Eguchi T, Aoyama, E, Moritani N, Oka M, Kawaki H, and Takigawa M.
  • Journal Title: J Cell Biochem Volume: 118 Issue: 11 Pages: 4033-4044
  • DOI: 10.1002/jcb.26059
  • Peer Reviewed / Open Access
• [Journal Article] Catabolic effects of FGF-1 on chondrocytes and its possible role in osteoarthritis. (2017)
  • Author(s): El-Seoudi A, Abd El Kader T, Nishida T, Eguchi T, Aoyama E, Takigawa M, Kubota S
  • Journal Title: J Cell Commun Signal. Volume: in press Issue: 3 Pages: 255-263
  • DOI: 10.1007/s12079-017-0384-8
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Novel role of CCN3 that maintains the differentiated phenotype of articular cartilage. (2017)
  • Author(s): Janune D, Abd El Kader T, Aoyama E, Nishida T, Tabata Y, Kubota S, Takigawa M
  • Journal Title: J Bone Miner Metab. Volume: in press Issue: 6 Pages: 582-597
  • DOI: 10.1007/s00774-016-0793-4
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Evaluation of Molecular Interaction between CCN2 Protein and Its Binding Partners by Surface Plasmon Resonance (SPR). (2017)
  • Author(s): Aoyama E, Takigawa M.
  • Journal Title: Methods Mol Biol. Volume: 1489 Pages: 169-176
• [Journal Article] Production of Recombinant CCN2 Protein in Escherichia coli. (2017)
  • Author(s): Aoyama E, Hattori T, Kubota S, Takigawa M.
  • Journal Title: Methods Mol Biol. Volume: 1489 Pages: 77-84
• [Journal Article] The Role of Sonic Hedgehog Signaling in Osteoclastogenesis and Jaw Bone Destruction. (2016)
  • Author(s): Shimo T, Matsumoto K, Takabatake K, Aoyama E, Takebe Y, Ibaragi S, Okui T, Kurio N, Takada H, Obata K, Pang P, Iwamoto M, Nagatsuka H, Sasaki A.
  • Journal Title: PLoS One. Volume: 11(3) Issue: 3 Pages: e0151731-e0151731
  • DOI: 10.1371/journal.pone.0151731
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Involvement of multiple CCN family members in platelets that support regeneration of joint tissues. (2016)
  • Author(s): Hara, C., Kubota, S., Nishida, T., Hiasa, M., Hattori, T., Aoyama, E., Moriyama, Y., Kamioka, H., Takigawa, M.
  • Journal Title: Mod. Rheumatol. Volume: なし Issue: 6 Pages: 1-10
  • DOI: 10.3109/14397595.2016.1155255
  • NAID: 120006358661
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Novel role of CCN3 that maintains the differentiated phenotype of articular cartilage. (2016)
  • Author(s): Janune D, Abd El Kader T, Aoyama E, Nishida T, Tabata Y, Kubota S, Takigawa M.
  • Journal Title: J Bone Miner Metab Volume: 印刷中
  • Peer Reviewed
• [Journal Article] CCN4/WISP-1 positively regulates chondrogenesis by controlling TGF-β3 function (2016)
  • Author(s): Yoshioka Y, Ono M, Maeda A, Kilts TM, Hara ES, Khattab H, Ueda J, Aoyama E, Oohashi T, Takigawa M, Young MF, Kuboki T.
  • Journal Title: Bone Volume: 83 Pages: 162-70
  • DOI: 10.1016/j.bone.2015.11.007
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Role of CCN2 in amino acid metabolism of chondrocytes (2016)
  • Author(s): Murase, Y,, Hattori, T., Aoyama, E., Nishida, T., Maeda-Uematsu, A., Kawaki, H., Lyons, K. M., Sasaki, A., Takigawa, M., Kubota, S
  • Journal Title: J. Cell Biochem Volume: 117 Issue: 4 Pages: 927-937
  • DOI: 10.1002/jcb.25377
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Involvement of multiple CCN family members in platelets that support regeneration of joint tissues (2016)
  • Author(s): Hara, C., Kubota, S., Nishida, T., Hiasa, M., Hattori, T., Aoyama, E., Moriyama, Y., Kamioka, H., Takigawa, M
  • Journal Title: Mod. Rheumatol Volume: In press
  • NAID: 120006358661
  • Peer Reviewed
• [Journal Article] Physical interaction of CCN2 with diverse growth factors involved in chondrocyte differentiation during endochondral ossification (2015)
  • Author(s): Khattab HM, Aoyama E, Kubota S, Takigawa M
  • Journal Title: J. Cell Commun. Signal. Volume: 未定 Issue: 3 Pages: 247-54
  • DOI: 10.1007/s12079-015-0290-x
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] CCN2 enhances RANKL-induced osteoclast differentiation via direct binding to RANK and OPG (2015)
  • Author(s): Eriko Aoyama , Satoshi Kubota , Hany Mohamed Khattab , Takashi Nishida , Masaharu Takigawa
  • Journal Title: Bone Volume: 73 Pages: 242-248
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] CCN family protein 2 (CCN2) promotes the early differentiation, but inhibits the terminal differentiation of skeletal myoblasts (2015)
  • Author(s): Nishida T, Kubota S, Aoyama E, Janune D, Lyons KM, Takigawa M.
  • Journal Title: J Biochem Volume: 157(2) Issue: 2 Pages: 91-100
  • DOI: 10.1093/jb/mvu056
  • NAID: 40020353020
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] 低出力超音波パルス（LIPUS）刺激による破骨細胞形成の抑制 (2017)
  • Author(s): 青山絵理子、久保田聡、山中信康、滝川正春
  • Organizer: 2017年度生命科学系学会合同年次大会
• [Presentation] CCN2結合因子GDF5の軟骨細胞における作用の解明 (2017)
  • Author(s): 井田すみれ、青山絵理子、久保田聡、滝川正春
  • Organizer: 第9回日本CCNファミリー研究会
• [Presentation] GDF5との結合を介したCCN2の軟骨分化促進作用 (2017)
  • Author(s): 井田すみれ、青山絵理子、久保田聡、滝川正春
  • Organizer: 第59回歯科基礎医学会学術大会
• [Presentation] CCN2結合因子CD302による破骨細胞成熟促進作用とその機序の解析 Mechanism of action of CCN2 binding protein CD302 ion osteoclast maturation (2016)
  • Author(s): 青山絵理子、久保田聡、滝川正春
  • Organizer: 第89回日本生化学会大会
  • Place of Presentation: 仙台
  • Year and Date: 2016-09-25
• [Presentation] 破骨細胞におけるCCN2結合性アクチン骨格制御因子CD302の作用機序の解明 (2016)
  • Author(s): 青山絵理子、久保田聡、滝川正春
  • Organizer: 第58回 歯科基礎医学会学術大会
  • Place of Presentation: 札幌
  • Year and Date: 2016-08-24
• [Presentation] The mechanism of osteoclast maturation mediated with CD302/DCL-1binding to CCN2 (2016)
  • Author(s): Eriko Aoyama, Satoshi Kubota, Masaharu Takigawa
  • Organizer: 第34回日本骨代謝学会学術集会 第3回アジア太平洋骨代謝学会議
  • Place of Presentation: Osaka
  • Year and Date: 2016-07-20
  • Int'l Joint Research
• [Presentation] Role of CCN2/CTGF-related CD302 in osteoclast maturation (2016)
  • Author(s): Eriko Aoyama, Satoshi Kubota, Masaharu Takigawa
  • Organizer: 94th General Session & Exhibition of the IADR
  • Place of Presentation: Seul, Korea
  • Year and Date: 2016-06-22
  • Int'l Joint Research
• [Presentation] A novel regulatory factor in osteoclastogenesis DCL-1/CD302: Significance of its binding to CCN2/CTGF (2016)
  • Author(s): Eriko Aoyama, Mitsuhiro Hoshijima, Satoshi Kubota, Masaharu Takigawa
  • Organizer: ECTS2016
  • Place of Presentation: Rome, Italy
  • Year and Date: 2016-05-14
  • Int'l Joint Research
• [Presentation] CCN2/CTGFとRANK/TRAILおよびosteoprotegerinとの分子間相互作用を介した破骨細胞形成促進機構 (2016)
  • Author(s): 青山絵理子、久保田聡、西田崇、滝川正春
  • Organizer: 第 33回 岡山免疫懇話会
  • Place of Presentation: 岡山
  • Year and Date: 2016-03-05
• [Presentation] CCN2結合因子CD302の破骨細胞機能制御作用 (2016)
  • Author(s): 青山絵理子、久保田聡、滝川正春
  • Organizer: 第 8回日本CCNファミリー研究会
  • Place of Presentation: 岡山
• [Presentation] 成熟破骨細胞のアクチンリング形成におけるCD302の機能とCCN2による制御 Novel role of CD302 in actin ring formation in mature osteoclasts and its interaction with CCN2 (2015)
  • Author(s): 青山絵理子、星島光博、服部高子、久保田聡、滝川正春
  • Organizer: 第88回日本生化学会大会
  • Place of Presentation: 神戸
  • Year and Date: 2015-12-01
• [Presentation] 破骨細胞分化における新規アクチン骨格制御因子としてのDCL-1/CD302の役割とCCN2との関連 (2015)
  • Author(s): 青山絵理子、星島光博、服部高子、久保田聡、滝川正春
  • Organizer: 第58回歯科基礎医学会
  • Place of Presentation: 新潟
  • Year and Date: 2015-09-11
• [Presentation] 新たな破骨細胞制御因子DCL-1/CD302の作用機構の解明とCCN2との関連。 (2015)
  • Author(s): 青山絵理子、服部高子、星島光博、久保田聡、滝川正春
  • Organizer: 第３３回日本骨代謝学会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2015-07-23
• [Presentation] 破骨細胞の成熟を制御する新規膜タンパク質CD302/DCL-1の機能とCCN2との結合。 (2015)
  • Author(s): 青山絵理子、服部高子、星島光博、久保田聡、滝川正春
  • Organizer: 第6回骨バイオサイエンス研究会
  • Place of Presentation: 岡山
  • Year and Date: 2015-07-04
• [Presentation] 成熟破骨細胞の形成におけるCD302/DCL-1の新機能とCCN2との関連。 (2015)
  • Author(s): 青山絵理子、星島光博、服部高子、久保田聡、滝川正春
  • Organizer: 第1回日本骨免疫学会
  • Place of Presentation: 沖縄
  • Year and Date: 2015-06-30
• [Book] Evaluation of molecular interaction between CCN family 2 protein and binding partners by surface plasmon resonance (SPR) in Method in Molecular Biology: CCN proteins (2016)
  • Author(s): Aoyama E., Takigawa M
  • Total Pages: 576
  • Publisher: Springer
• [Book] Production of recombinant CCN family2 protein in Escherichia. coli. in Method in Molecular Biology: CCN proteins (2016)
  • Author(s): Aoyama E., Hattori T., Kubota S., Takigawa M
  • Total Pages: 576
  • Publisher: Springer