CCN3 and bone marrow cells
Tóm tắt
CCN3 expression was observed in a broad variety of tissues from the early stage of development. However, a kind of loss of function in mice (CCN3 del VWC domain -/-) demonstrated mild abnormality, which indicates that CCN3 may not be critical for the normal embryogenesis as a single gene. The importance of CCN3 in bone marrow environment becomes to be recognized by the studies of hematopoietic stem cells and Chronic Myeloid Leukemia cells. 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 new antibody although they are a very few populations. We investigated the expression pattern of CCN3 in the cultured bone marrow derived mesenchymal stem cells and found its preference for osteogenic differentiation. From the analyses of in vitro experiment 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. Secreted CCN3 from Kusa cells inhibited the differentiation of osteoblasts in separate culture, which indicates the paracrine manner of CCN3 activity. CCN3 may also affect the extracellular environment of the niche for hematopoietic stem cells.
Tài liệu tham khảo
Allan EH, Ho PW, Umezawa A, Hata J, Makishima F, Gillespie MT, Martin TJ (2003) Differentiation potential of a mouse bone marrow stromal cell line. J Cell Biochem 90(1):158–169
Brigstock DR, Goldschmeding R, Katsube KI, Lam SC, Lau LF, 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
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
Calvi LM, Adams GB, Weibrecht KW, Weber JM, Olson DP, Knight MC, Martin RP, Schipani E, Divieti P, Bringhurst FR, Milner LA, Kronenberg HM, Scadden DT (2003) Osteoblastic cells regulate the haematopoietic stem cell niche. Nature 425(6960):841–846
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
Chiou MJ, Chao TT, Wu JL, Kuo CM, Chen JY (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
Erwin WM (2008) The Notochord, Notochordal cell and CTGF/CCN-2: ongoing activity from development through maturation. J Cell Commun Signal 2(3–4):59–65
Fukunaga-Kalabis M, Martinez G, Telson SM, Liu ZJ, Balint K, Juhasz I, Elder DE, Perbal B, Herlyn M (2008) Downregulation of CCN3 expression as a potential mechanism for melanoma progression. Oncogene 27(18):2552–2560
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
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
Hamburger V (1992) The stage series of the chick embryo. Dev Dyn 195(4):273–275
Harigaya K (1987) Fibrocytic bone marrow stromal cells and hematopoiesis. Nippon Ketsueki Gakkai Zasshi 50(8):1499–1509
Haylock DN, Nilsson SK (2005) Stem cell regulation by the hematopoietic stem cell niche. Cell Cycle 4(10):1353–1355
Heath E, Tahri D, Andermarcher E, Schofield P, Fleming S, Boulter CA (2008) Abnormal skeletal and cardiac development, cardiomyopathy, muscle atrophy and cataracts in mice with a targeted disruption of the Nov (Ccn3) gene. BMC Dev Biol 8(1):18
Ivkovic S, Yoon BS, Popoff SN, Safadi FF, Libuda DE, Stephenson RC, Daluiski A, Lyons KM (2003) Connective tissue growth factor coordinates chondrogenesis and angiogenesis during skeletal development. Development 130(12):2779–2791
Katsube K, Chuai ML, Liu YC, 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
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
Katsuki Y, Sakamoto K, Minamizato T, Makino H, Umezawa A, Ikeda MA, 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
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
Kohyama J, Abe H, Shimazaki T, Koizumi A, Nakashima K, Gojo S, Taga T, Okano H, Hata J, Umezawa A (2001) Brain from bone: efficient “meta-differentiation” of marrow stroma-derived mature osteoblasts to neurons with Noggin or a demethylating agent. Differentiation 68(4–5):235–244
Lo Celso C, Fleming HE, Wu JW, Zhao CX, Miake-Lye S, Fujisaki J, Cote D, Rowe DW, Lin CP, Scadden DT (2009) Live-animal tracking of individual haematopoietic stem/progenitor cells in their niche. Nature 457(7225):92–96
Makino S, Fukuda K, Miyoshi S, Konishi F, Kodama H, Pan J, Sano M, Takahashi T, Hori S, Abe H, Hata J, Umezawa A, Ogawa S (1999) Cardiomyocytes can be generated from marrow stromal cells in vitro. J Clin Invest 103(5):697–705
McCallum L, Price S, Planque N, Perbal B, Pierce A, Whetton AD, Irvine AE (2006) A novel mechanism for BCR-ABL action: stimulated secretion of CCN3 is involved in growth and differentiation regulation. Blood 108(5):1716–1723
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
Mo FE, Muntean AG, Chen CC, Stolz DB, Watkins SC, Lau LF (2002) CYR61 (CCN1) is essential for placental development and vascular integrity. Mol Cell Biol 22(24):8709–8720
Morikawa S, Mabuchi Y, Niibe K, Suzuki S, Nagoshi N, Sunabori T, Shimmura S, Nagai Y, Nakagawa T, Okano H, Matsuzaki Y (2009) Development of mesenchymal stem cells partially originate from the neural crest. Biochem Biophys Res Commun 379(4):1114–1119
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
Papalopulu N, Clarke JD, Bradley L, Wilkinson D, Krumlauf R, Holder N (1991) Retinoic acid causes abnormal development and segmental patterning of the anterior hindbrain in Xenopus embryos. Development 113(4):1145–1158
Parisi MS, Gazzerro E, Rydziel S, Canalis E (2006) Expression and regulation of CCN genes in murine osteoblasts. Bone 38(5):671–677
Perbal B (2007) CCN3-mutant mice are distinct from CCN3-null mice. J Cell Commun Signal 1(3–4):229–230
Rangarajan A, Talora C, Okuyama R, Nicolas M, Mammucari C, Oh H, Aster JC, Krishna S, Metzger D, Chambon P, Miele L, Aguet M, Radtke F, Dotto GP (2001) Notch signaling is a direct determinant of keratinocyte growth arrest and entry into differentiation. Embo J 20(13):3427–3436
Raya A, Kawakami Y, Rodriguez-Esteban C, Buscher D, Koth CM, Itoh T, Morita M, Raya RM, Dubova I, Bessa JG, de la Pompa JL, Belmonte JC (2003) Notch activity induces Nodal expression and mediates the establishment of left–right asymmetry in vertebrate embryos. Genes Dev 17(10):1213–1218
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
Sakamoto K, Nakamura H, Takagi M, Takeda S, Katsube K (1998) Ectopic expression of lunatic Fringe leads to downregulation of Serrate-1 in the developing chick neural tube; analysis using in ovo electroporation transfection technique. FEBS Lett 426(3):337–341
Sakamoto K, Yamaguchi S, Ando R, Miyawaki A, Kabasawa Y, Takagi M, Li CL, 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
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
Sharov AA, Piao Y, Matoba R, Dudekula DB, Qian Y, VanBuren V, Falco G, Martin PR, Stagg CA, Bassey UC, Wang Y, Carter MG, Hamatani T, Aiba K, Akutsu H, Sharova L, Tanaka TS, Kimber WL, Yoshikawa T, Jaradat SA, Pantano S, Nagaraja R, Boheler KR, Taub D, Hodes RJ, Longo DL, Schlessinger D, Keller J, Klotz E, Kelsoe G, Umezawa A, Vescovi AL, Rossant J, Kunath T, Hogan BL, Curci A, D'Urso M, Kelso J, Hide W, Ko MS (2003) Transcriptome analysis of mouse stem cells and early embryos. PLoS Biol 1(3):E74
Shimomura T, Yoshida Y, Sakabe T, Ishii K, Gonda K, Murai R, Takubo K, Tsuchiya H, Hoshikawa Y, Kurimasa A, Hisatome I, Uyama T, Umezawa A, Shiota G (2007) Hepatic differentiation of human bone marrow-derived UE7T-13 cells: effects of cytokines and CCN family gene expression. Hepatol Res 37(12):1068–1079
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
Umezawa A, Tachibana K, Harigaya K, Kusakari S, Kato S, Watanabe Y, Takano T (1991) Colony-stimulating factor 1 expression is down-regulated during the adipocyte differentiation of H-1/A marrow stromal cells and induced by cachectin/tumor necrosis factor. Mol Cell Biol 11(2):920–927
Umezawa A, Maruyama T, Segawa K, Shadduck RK, Waheed A, Hata J (1992) Multipotent marrow stromal cell line is able to induce hematopoiesis in vivo. J Cell Physiol 151(1):197–205
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
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 PG (2009) Cell-cycle restriction limits DNA damage and maintains self-renewal of leukaemia stem cells. Nature 457(7225):51–56
Watanabe Y, Nakamura H (2000) Control of chick tectum territory along dorsoventral axis by Sonic hedgehog. Development 127(5):1131–1140
Zhang J, Niu C, Ye L, Huang H, He X, Tong WG, Ross J, Haug J, Johnson T, Feng JQ, Harris S, Wiedemann LM, Mishina Y, Li L (2003) Identification of the haematopoietic stem cell niche and control of the niche size. Nature 425(6960):836–841