2006 Fiscal Year Final Research Report Summary
Role of CCN2 as a trans-modulator in the integrated development of bone, cartilage and hematopoietic systems
| Project/Area Number |
17591938
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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 |
Functional basic dentistry
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| Research Institution | Okayama University |
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Principal Investigator |
KUBOTA Satoshi Okayama Univ., Grad. Sch. Med. Dent. & Pharmac. Sci., Assoc. Prof., 大学院医歯薬学総合研究科, 助教授 (90221936)
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| Co-Investigator(Kenkyū-buntansha) |
TAKIGAWA Masaharu Okayama Univ., Grad. Sch. Med. Dent. & Pharmac. Sci., Prof., 大学院医歯薬学総合研究科, 教授 (20112063)
HATTORI Takako Okayama Univ., Grad. Sch. Med. Dent. & Pharmac. Sci., Assist., 大学院医歯薬学総合研究科, 助手 (00228488)
NISHIDA Takashi Okayama Univ., Grad. Sch. Med. Dent. & Pharmac. Sci., Assist., 大学院医歯薬学総合研究科, 助手 (30322233)
AOYAMA Eriko Okayama Univ., Dent. Sch., Res. Tech., 歯学部, 教務員 (10432650)
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| Project Period (FY) |
2005 – 2006
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| Keywords | CCN / CTGF / bone marrow / cartilage / hematopoiesis |
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| Research Abstract |
1. Investigation on the production and distribution of CCN2 in hematopoietic cells in bone marrow
Identification of CCN2 producers and target cells : Based on the fact that platelets harbor a vast amount of CCN2, we hypothesized megakaryocytes as the major CCN2 producer. Initially, we evaluated the CCN2 mRNA expression and protein production by a megakaryocytic CMK cell line, but failed to detect them. Next, we isolated human hematopoietic stem cells and drove them differentiate into megakaryocytes in vitro. As a result, we could detect ccn2 mRNA at the final stage of the differentiation of megakaryocytes in vitro. In addition, by analyzing bone marrow histochemically, a putative CCN2-associated cell surface receptor, EphA4, was detected on megakaryocytes, which may contribute to the uptake of CCN2 from outside upon the formation of platelets.
Evaluation of the effects of CCN2 on hematopoietic cells : We showed that mesenchymal knocking-down of ccn2 expression resulted in the repression of osteoclast development from the macrophage-monocyte lineage. This finding strongly indicates that osteoclast progenitor is one of the CCN2 target cells.
2. Analysis of the interaction between CCN2 and other cytokines in bone marrow.
First of all, we for the first time clarified that CCN2 provoked the gene expression of M-CSF, which is critically required for the differentiation of the cells in the monocyte lineage, in chondrocytes. Subsequently, by using a bacteriophage-display system, we screened dodecapeptides that specifically interacted with each module of tetramodular CCN2 molecule. With the data obtained, common peptide binding motifs were extracted in silico. We synthesized a peptide with one such motif and found that it actually repressed the effects of CCN2 on chondrocytes in vitro.
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