The Effect of Growth Differentiation Factor-5, 6, 7 in Chondrogenic Cell Differentiation of ATDC-5
American Journal of BioScience
Volume 2, Issue 5, September 2014, Pages: 182-186
Received: Jul. 31, 2014;
Accepted: Aug. 25, 2014;
Published: Sep. 10, 2014
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Yuji a Hatakeyam, Section of Functional Structure, Department of Morphological Biology, Fukuoka Dental College, Fukuoka, Japan
Yuko Matsuda, Section of Orthodontics, Department of Oral Growth and Development, Fukuoka Dental College, Fukuoka, Japan
Junko Hatakeyama, Section of Operative Dentistry, Department of Odontology, Fukuoka Dental College, Fukuoka, Japan
Kyoko Oka, Section of Pediatric Dentistry, Department of Oral Growth and Development, Fukuoka Dental College, Fukuoka, Japan
Hisashi Anan, Section of Operative Dentistry, Department of Odontology, Fukuoka Dental College, Fukuoka, Japan
Eichi Tsuruga, Department of Pathologic Aanalysis, Division of Medical Sciences, Hirosaki University Graduate School of Health Sciences, Hirosaki, Japan
Tetsuichiro Inai, Section of Functional Structure, Department of Morphological Biology, Fukuoka Dental College, Fukuoka, Japan
Hiroyuki Ishikawa, Section of Orthodontics, Department of Oral Growth and Development, Fukuoka Dental College, Fukuoka, Japan
Yoshihiko Sawa, Section of Functional Structure, Department of Morphological Biology, Fukuoka Dental College, Fukuoka, Japan
The proteins known as growth differentiation factors (GDFs) are members of the BMP family; GDF-5, -6, and -7 play important roles in skeletogenesis, especially with regard to chondrogenesis. The functional differences among these GDFs in chondrogenesis and chondrocyte cell differentiation remains unclear. Here, we attempt to assay cell proliferation, the production of chondrogenic matrices indicated by alcian blue intensity, and the profile of a chondrogenic cell differentiation marker gene in a cell culture of the chondrogenic cell line ATDC5 with or without recombinant mouse GDF-5, -6, and -7. After 24h culture, the ATDC5 cell number was significantly decreased in the exogenous presence of each GDF compared with a control culture absent all GDFs. On the other hand, alcian blue staining of cell cultures after 2w culture showed significantly increased intensity compared with that of the control. The expression levels of the chondrogenic cell differentiation marker genes Sox9 and aggrecan were increased after 24h and 48h culture by all GDFs, but were significantly increased in the presence of GDF-5 compared with the presence of GDF-6 or -7. These findings suggest that GDF-5, -6, and -7 could all promote chondrogenic cell differentiation of ATDC5, but GDF-5 may induce chondrogenic genes more potently than GDF-6 and -7 do.
Yuji a Hatakeyam,
The Effect of Growth Differentiation Factor-5, 6, 7 in Chondrogenic Cell Differentiation of ATDC-5, American Journal of BioScience.
Vol. 2, No. 5,
2014, pp. 182-186.
Storm EE., Huynh TV., Copeland NG., Jenkins NA., Kingsley DM., Lee SJ. (1994) Limb alterations in brachypodism mice due to mutations in a new member of the TGF beta-superfamily. Nature. 368(6472):639-43.
Sanna S., Jackson AU., Nagaraja R., Willer CJ., Chen WM., Bonnycastle LL., Shen H., Timpson N., Lettre G., Usala G., Chines PS., Stringham HM., Scott LJ., Dei M., Lai S., Albai G., Crisponi L., Naitza S., Doheny KF., Pugh EW., Ben-Shlomo Y., Ebrahim S., Lawlor DA., Bergman RN., Watanabe RM., Uda M., Tuomilehto J., Coresh J., Hirschhorn JN., Shuldiner AR., Schlessinger D., Collins FS., Davey Smith G., Boerwinkle E., Cao A., Boehnke M., Abecasis GR., Mohlke KL. (2008) Common variants in the GDF5-UQCC region are associated with variation in human height. Nat Genet. 40(2):198-203.
Yoshimoto T., Yamamoto M., Kadomatsu H., Sakoda K., Yonamine Y., Izumi Y. (2006) Recombinant human growth/differentiation factor-5 (rhGDF-5) induced bone formation in murine calvariae. J Periodontal Res. 41(2):140-7.
Hatakeyama Y., Tuan RS., Shum L. (2004) Distinct functions of BMP4 and GDF5 in the regulation of chondrogenesis. J Cell Biochem. 91(6):1204-17.
Erlacher L., Ng CK., Ullrich R., Krieger S., Luyten FP. (1998) Presence of cartilage-derived morphogenetic proteins in articular cartilage and enhancement of matrix replacement in vitro. Arthritis Rheum. 41(2):263-73.
Shen B., Bhargav D., Wei A., Williams LA., Tao H., Ma DD., Diwan AD. (2009) BMP-13 emerges as a potential inhibitor of bone formation. Int J Biol Sci. 5(2):192-200
Yeh LC., Lee JC. (2010) Effects of cartilage-derived morphogenetic protein-3 on the expression of chondrogenic and osteoblastic markers in the pluripotent mesenchymal C3H10T1/2 cell line. Growth Factors. 28(2):117-28.
Mikic B., Ferreira MP., Battaglia TC., Hunziker EB. (2008) Accelerated hypertrophic chondrocyte kinetics in GDF-7 deficient murine tibial growth plates. J Orthop Res. 26(7):986-90.
Gooch KJ, Blunk T, Courter DL, Sieminski AL, Vunjak-Novakovic G, Freed LE. (2002) Bone morphogenetic proteins-2, -12, and -13 modulate in vitro development of engineered cartilage. Tissue Eng. 8(4):591-601.
Hatakeyama Y., Hatakeyama J., Takahashi A., Oka K., Tsuruga E., Inai T., Sawa Y. (2011) The effect of valproic acid on mesenchymal pluripotent cell proliferation and differentiation in extracellular matrices. Drug Target Insights. 5:1-9.
Nagata M., Nuckolls GH., Wang X., Shum L., Seki Y., Kawase T., Takahashi K., Nonaka K., Takahashi I., Noman AA., Suzuki K., Slavkin HC. (2011) The primary site of the acrocephalic feature in Apert Syndrome is a dwarf cranial base with accelerated chondrocytic differentiation due to aberrant activation of the FGFR2 signaling. Bone. 48(4):847-56.
Atsumi T, Miwa Y, Kimata K, Ikawa Y. (1990) A chondrogenic cell line derived from a differentiating culture of AT805 teratocarcinoma cells. Cell Differ Dev. 30(2):109-16.
Altaf FM., Hering TM., Kazmi NH., Yoo JU., Johnstone B. (2006) Ascorbate-enhanced chondrogenesis of ATDC5 cells Eur Cell Mater. 12:64-9
Nakamura K, Shirai T, Morishita S, Uchida S, Saeki-Miura K, Makishima F. (1999) p38 mitogen-activated protein kinase functionally contributes to chondrogenesis induced by growth/differentiation factor-5 in ATDC5 cells. Exp Cell Res. 250(2):351-63.
Han F., Adams CS., Tao Z., Williams CJ., Zaka R., Tuan RS., Norton PA., Hickok NJ. (2005) Transforming growth factor-beta1 (TGF-beta1) regulates ATDC5 chondrogenic differentiation and fibronectin isoform expression. Cell Biochem. 95(4):750-62.
Wright E., Hargrave MR., Christiansen J., Cooper L., Kun J., Evans T., Gangadharan U., Greenfield A., Koopman P. (1995) The Sry-related gene Sox9 is expressed during chondrogenesis in mouse embryos. Nat Genet. 9(1):15-20.
Sekiya I, Tsuji K, Koopman P, Watanabe H, Yamada Y, Shinomiya K, Nifuji A, Noda M. (2000) SOX9 enhances aggrecan gene promoter/enhancer activity and is up-regulated by retinoic acid in a cartilage-derived cell line, TC6. J Biol Chem. 275(15):10738-44.
Xia D., Sumita Y., Liu Y., Tai Y., Wang J., Uehara M., Agata H., Kagami H., Fan Z., Asahina I., Wang S., Tran SD. (2013) GDFs promote tenogenic characteristics on human periodontal ligament-derived cells in culture at late passages. Growth Factors. 31(5):165-73.
Valcourt U1, Ronzière MC, Winkler P, Rosen V, Herbage D, Mallein-Gerin F. (1999) Different effects of bone morphogenetic proteins 2, 4, 12, and 13 on the expression of cartilage and bone markers in the MC615 chondrocyte cell line. Exp Cell Res. 251(2):264-74.