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CCN Proteins in Health and Disease pp 111–119Cite as

The Role of CCN3 in Mesenchymal Stem Cells

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Abstract

CCN3 expression was observed in a broad variety of tissues from the early stage of development. CCN3 expression in bone marrow has been denied by several investigations, but we found CCN3 positive stromal and hematopoietic cells at bone extremities with a newly raised antibody, although they are a very few population in number. We investigated the expression pattern of CCN3 in the cultured bone marrow derived mesenchymal stem cells and found a preference in osteogenic differentiation. From the analyses of in vitro experiments using an osteogenic mesenchymal stem cell line, Kusa-A1, we found that CCN3 downregulates osteogenesis by two different pathways: suppression of BMP and stimulation of Notch. This effect was also transmitted to osteoblasts in separate cultures, which indicates the paracrine manner of CCN3 activity. CCN3 may also affect the extracellular environment of the niche for hematopoietic stem cells.

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References

  • Brigstock D.R., Goldschmeding R., Katsube K.I., Lam S.C., Lau L.F., Lyons K., Naus C., Perbal B., Riser B., Takigawa M., Yeger H. (2003). Proposal for a unified CCN nomenclature. Mol Pathol 56(2): 127–128.

    Article  CAS  PubMed  Google Scholar 

  • Byrd N., Becker S., Maye P., Narasimhaiah R., St-Jacques B., Zhang X., McMahon J., McMahon A., Grabel L. (2002). Hedgehog is required for murine yolk sac angiogenesis. Development 129(2): 361–372.

    CAS  PubMed  Google Scholar 

  • Calvi L.M., Adams G.B., Weibrecht K.W., Weber J.M., Olson D.P., Knight M.C., Martin R.P., Schipani E., Divieti P., Bringhurst F.R., Milner L.A., Kronenberg H.M., Scadden D.T. (2003). Osteoblastic cells regulate the haematopoietic stem cell niche. Nature 425(6960): 841–846.

    Article  CAS  PubMed  Google Scholar 

  • Caprioli A., Minko K., Drevon C., Eichmann A., Dieterlen-Lievre F., Jaffredo T. (2001). Hemangioblast commitment in the avian allantois: cellular and molecular aspects. Dev Biol 238(1): 64–78.

    Article  CAS  PubMed  Google Scholar 

  • Chiou M.J., Chao T.T., Wu J.L., Kuo C.M., Chen J.Y. (2006). The physiological role of CTGF/CCN2 in zebrafish notochond development and biological analysis of the proximal promoter region. Biochem Biophys Res Commun 349(2): 750–758.

    Article  CAS  PubMed  Google Scholar 

  • Erwin W.M. (2008). The notochord, notochordal cell and CTGF/CCN-2: ongoing activity from development through maturation. J Cell Commun Signal 2(3–4): 59–65.

    Google Scholar 

  • Fukunaga-Kalabis M., Martinez G., Telson S.M., Liu Z.J., Balint K., Juhasz I., Elder D.E., Perbal B., Herlyn M. (2008). Downregulation of CCN3 expression as a potential mechanism for melanoma progression. Oncogene 27(18): 2552–2560.

    Article  CAS  PubMed  Google Scholar 

  • Grabel L., Becker S., Lock L., Maye P., Zanders T. (1998). Using EC and ES cell culture to study early development: recent observations on Indian hedgehog and Bmps. Int J Dev Biol 42(7): 917–925.

    CAS  PubMed  Google Scholar 

  • Gupta R., Hong D., Iborra F., Sarno S., Enver T. (2007). NOV (CCN3) functions as a regulator of human hematopoietic stem or progenitor cells. Science 316(5824): 590–593.

    Article  CAS  PubMed  Google Scholar 

  • Harigaya K. (1987). Fibrocytic bone marrow stromal cells and hematopoiesis. Nippon Ketsueki Gakkai Zasshi 50(8): 1499–1509.

    CAS  PubMed  Google Scholar 

  • Haylock D.N., Nilsson S.K. (2005). Stem cell regulation by the hematopoietic stem cell niche. Cell Cycle 4(10): 1353–1355.

    CAS  PubMed  Google Scholar 

  • Katsube K., Chuai M.L., Liu Y.C., Kabasawa Y., Takagi M., Perbal B., Sakamoto K. (2001). The expression of chicken NOV, a member of the CCN gene family, in early stage development. Brain Res Gene Expr Patterns 1(1): 61–65.

    Article  CAS  PubMed  Google Scholar 

  • Katsube K., Sakamoto K., Tamamura Y., Yamaguchi A. (2009). Role of CCN, a vertebrate specific gene family, in development. Dev Growth Differ 51(1): 55–67.

    Article  CAS  PubMed  Google Scholar 

  • Katsuki Y., Sakamoto K., Minamizato T., Makino H., Umezawa A., Ikeda M.A., Perbal B., Amagasa T., Yamaguchi A., Katsube K. (2008).Inhibitory effect of CT domain of CCN3/NOV on proliferation and differentiation of osteogenic mesenchymal stem cells, Kusa-A1. Biochem Biophys Res Commun 368(3): 808–814.

    Article  CAS  PubMed  Google Scholar 

  • Kawashima N., Shindo K., Sakamoto K., Kondo H., Umezawa A., Kasugai S., Perbal B., Suda H., Takagi M., Katsube K. (2005). Molecular and cell biological properties of mouse osteogenic mesenchymal progenitor cells, Kusa. J Bone Miner Metab 23(2): 123–133.

    Article  CAS  PubMed  Google Scholar 

  • Lo Celso C., Fleming H.E., Wu J.W., Zhao C.X., Miake-Lye S., Fujisaki J., Cote D., Rowe D.W., Lin C.P., Scadden D.T. (2009). Live-animal tracking of individual haematopoietic stem/progenitor cells in their niche. Nature 457(7225): 92–96.

    Article  CAS  PubMed  Google Scholar 

  • McCallum L., Price S., Planque N., Perbal B., Pierce A., Whetton A.D., Irvine A.E. (2006). A novel mechanism for BCR-ABL action: stimulated secretion of CCN3 is involved in growth and differentiation regulation. Blood 108(5): 1716–1723.

    Article  CAS  PubMed  Google Scholar 

  • Minamizato T., Sakamoto K., Liu T., Kokubo H., Katsube K., Perbal B., Nakamura S., Yamaguchi A. (2007). CCN3/NOV inhibits BMP-2-induced osteoblast differentiation by interacting with BMP and Notch signaling pathways. Biochem Biophys Res Commun 354(2): 567–573.

    Article  CAS  PubMed  Google Scholar 

  • Mo F.E., Muntean A.G., Chen C.C., Stolz D.B., Watkins S.C., Lau L.F. (2002). CYR61 (CCN1) is essential for placental development and vascular integrity. Mol Cell Biol 22(24): 8709–8720.

    Article  CAS  PubMed  Google Scholar 

  • Oka M., Kubota S., Kondo S., Eguchi T., Kuroda C., Kawata K., Minagi S., Takigawa M. (2007). Gene expression and distribution of connective tissue growth factor (CCN2/CTGF) during secondary ossification center formation. J Histochem Cytochem 55(12): 1245–1255.

    Article  CAS  PubMed  Google Scholar 

  • Parisi M.S., Gazzerro E., Rydziel S., Canalis E. (2006). Expression and regulation of CCN genes in murine osteoblasts. Bone 38(5): 671–677.

    Article  CAS  PubMed  Google Scholar 

  • Rangarajan A., Talora C., Okuyama R., Nicolas M., Mammucari C., Oh H., Aster J.C., Krishna S., Metzger D., Chambon P., Miele L., Aguet M., Radtke F., Dotto G.P. (2001). Notch signaling is a direct determinant of keratinocyte growth arrest and entry into differentiation. Embo J 20(13): 3427–3436.

    Article  CAS  PubMed  Google Scholar 

  • Rydziel S., Stadmeyer L., Zanotti S., Durant D., Smerdel-Ramoya A., Canalis E. (2007). Nephroblastoma overexpressed (Nov) inhibits osteoblastogenesis and causes osteopenia. J Biol Chem 282(27): 19762–19772.

    Article  CAS  PubMed  Google Scholar 

  • Sakamoto K., Yamaguchi S., Ando R., Miyawaki A., Kabasawa Y., Takagi M., Li C.L., Perbal B., Katsube K. (2002). The nephroblastoma overexpressed gene (NOV/ccn3) protein associates with Notch1 extracellular domain and inhibits myoblast differentiation via Notch signaling pathway. J Biol Chem 277(33): 29399–29405.

    Article  CAS  PubMed  Google Scholar 

  • Schutze N., Noth U., Schneidereit J., Hendrich C., Jakob F. (2005). Differential expression of CCN-family members in primary human bone marrow-derived mesenchymal stem cells during osteogenic, chondrogenic and adipogenic differentiation. Cell Commun Signal 3(1): 5.

    Article  PubMed  Google Scholar 

  • Soret J., Dambrine G., Perbal B. (1989). Induction of nephroblastoma by myeloblastosis-associated virus type 1: state of proviral DNAs in tumor cells. J Virol 63(4): 1803–1807.

    CAS  PubMed  Google Scholar 

  • van den Bos C., Silverstetter S., Murphy M., Connolly T. (1998). p21(cip1) rescues human mesenchymal stem cells from apoptosis induced by low-density culture. Cell Tissue Res 293(3): 463–470.

    Article  PubMed  Google Scholar 

  • Viale A., De Franco F., Orleth A., Cambiaghi V., Giuliani V., Bossi D., Ronchini C., Ronzoni S., Muradore I., Monestiroli S., Gobbi A., Alcalay M., Minucci S., Pelicci P.G. (2009). Cell-cycle restriction limits DNA damage and maintains self-renewal of leukaemia stem cells. Nature 457(7225): 51–56.

    Article  CAS  PubMed  Google Scholar 

  • Zhang J., Niu C., Ye L., Huang H., He X., Tong W.G., Ross J., Haug J., Johnson T., Feng J.Q., Harris S., Wiedemann L.M., Mishina Y., Li L. (2003). Identification of the haematopoietic stem cell niche and control of the niche size. Nature 425(6960): 836–841.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgement

This work was supported by Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science to KK (15390552 and 20592135).

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Authors and Affiliations

  1. Oral Pathology, Graduate School of Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8549, Japan

    Ken-Ichi Katsube

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  1. Ken-Ichi Katsube
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Correspondence to Ken-Ichi Katsube .

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Editors and Affiliations

  1. Med Sci-I 6447, Ann Arbor, 48109, USA

    Annick Perbal

  2. Shikata-Cho 2-5-1, Okayama, 700-8525, Japan

    Masaharu Takigawa

  3. Palais du Grand Large, International CCN Society, Saint-Malo, France

    Bernard Perbal

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Katsube, KI. (2010). The Role of CCN3 in Mesenchymal Stem Cells. In: Perbal, A., Takigawa, M., Perbal, B. (eds) CCN Proteins in Health and Disease. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-3779-4_9

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