Chondrogenic differentiation of clonal mouse embryonic cell line ATDC5 in vitro: differentiation-dependent gene expression of parathyroid hormone (PTH)/PTH-related peptide receptor

doi:10.1083/jcb.133.2.457

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Chondrogenic differentiation of clonal mouse embryonic cell line ATDC5 in vitro: differentiation-dependent gene expression of parathyroid hormone (PTH)/PTH-related peptide receptor

C Shukunami, C Shigeno, T Atsumi, K Ishizeki, F Suzuki and Y Hiraki
Department of Biochemistry, Osaka University Faculty of Dentistry, Japan.

The regulatory role of parathyroid hormone (PTH)/PTH-related peptide (PTHrP) signaling has been implicated in embryonic skeletal development. Here, we studied chondrogenic differentiation of the mouse embryonal carcinoma-derived clonal cell line ATDC5 as a model of chondrogenesis in the early stages of endochondral bone development. ATDC5 cells retain the properties of chondroprogenitor cells, and rapidly proliferate in the presence of 5% FBS. Insulin (10 micrograms/ml) induced chondrogenic differentiation of the cells in a postconfluent phase through a cellular condensation process, resulting in the formation of cartilage nodules, as evidenced by expression of type II collagen and aggrecan genes. We found that differentiated cultures of ATDC5 cells abundantly expressed the high affinity receptor for PTH (Mr approximately 80 kD; Kd = 3.9 nM; 3.2 x 10(5) sites/cell). The receptors on differentiated cells were functionally active, as evidenced by a PTH-dependent activation of adenylate cyclase. Specific binding of PTH to cells markedly increased with the formation of cartilage nodules, while undifferentiated cells failed to show specific binding of PTH. Northern blot analysis indicated that expression of the PTH/PTHrP receptor gene became detectable at the early stage of chondrogenesis of ATDC5 cells, preceding induction of aggrecan gene expression. Expression of the PTH/PTHrP receptor gene was undetectable in undifferentiated cells. The level of PTH/PTHrP receptor mRNA was markedly elevated parallel to that of type II collagen mRNA. These lines of evidence suggest that the expression of functional PTH/PTHrP receptor is associated with the onset of chondrogenesis. In addition, activation of the receptor by exogenous PTH or PTHrP significantly interfered with cellular condensation and the subsequent formation of cartilage nodules, suggesting a novel site of PTHrP action.
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Mori, H., Shukunami, C., Furuyama, A., Notsu, H., Nishizaki, Y., Hiraki, Y. (2007). Immobilization of Bioactive Fibroblast Growth Factor-2 into Cubic Proteinous Microcrystals (Bombyx mori Cypovirus Polyhedra) That Are Insoluble in a Physiological Cellular Environment. J. Biol. Chem. 282: 17289-17296 [Abstract] [Full Text]
Kondo, S., Shukunami, C., Morioka, Y., Matsumoto, N., Takahashi, R., Oh, J., Atsumi, T., Umezawa, A., Kudo, A., Kitayama, H., Hiraki, Y., Noda, M. (2007). Dual effects of the membrane-anchored MMP regulator RECK on chondrogenic differentiation of ATDC5 cells. J. Cell Sci. 120: 849-857 [Abstract] [Full Text]
Sakai, K., Kimata, K., Sato, T., Gotoh, M., Narimatsu, H., Shinomiya, K., Watanabe, H. (2007). Chondroitin Sulfate N-Acetylgalactosaminyltransferase-1 Plays a Critical Role in Chondroitin Sulfate Synthesis in Cartilage. J. Biol. Chem. 282: 4152-4161 [Abstract] [Full Text]
Hoogendam, J., Parlevliet, E., Miclea, R., Lowik, C. W. G. M., Wit, J. M., Karperien, M. (2006). Novel Early Target Genes of Parathyroid Hormone-Related Peptide in Chondrocytes. Endocrinology 147: 3141-3152 [Abstract] [Full Text]
Kamiya, N., Watanabe, H., Habuchi, H., Takagi, H., Shinomura, T., Shimizu, K., Kimata, K. (2006). Versican/PG-M Regulates Chondrogenesis as an Extracellular Matrix Molecule Crucial for Mesenchymal Condensation. J. Biol. Chem. 281: 2390-2400 [Abstract] [Full Text]
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Gori, F., Demay, M. B. (2004). BIG-3, a Novel WD-40 Repeat Protein, Is Expressed in the Developing Growth Plate and Accelerates Chondrocyte Differentiation in Vitro. Endocrinology 145: 1050-1054 [Abstract] [Full Text]
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Miyazaki, K., Kawamoto, T., Tanimoto, K., Nishiyama, M., Honda, H., Kato, Y. (2002). Identification of Functional Hypoxia Response Elements in the Promoter Region of the DEC1 and DEC2 Genes. J. Biol. Chem. 277: 47014-47021 [Abstract] [Full Text]
Tanaka, K., Tsumaki, N., Kozak, C. A., Matsumoto, Y., Nakatani, F., Iwamoto, Y., Yamada, Y. (2002). A Kruppel-Associated Box-Zinc Finger Protein, NT2, Represses Cell-Type-Specific Promoter Activity of the {alpha}2(XI) Collagen Gene. Mol. Cell. Biol. 22: 4256-4267 [Abstract] [Full Text]
Newman, B., Gigout, L. I., Sudre, L., Grant, M. E., Wallis, G. A. (2001). Coordinated expression of matrix Gla protein is required during endochondral ossification for chondrocyte survival. JCB 154: 659-666 [Abstract] [Full Text]
Tanaka, K., Matsumoto, Y., Nakatani, F., Iwamoto, Y., Yamada, Y. (2000). A Zinc Finger Transcription Factor, alpha A-Crystallin Binding Protein 1, Is a Negative Regulator of the Chondrocyte-Specific Enhancer of the alpha 1(II) Collagen Gene. Mol. Cell. Biol. 20: 4428-4435 [Abstract] [Full Text]
Palmer, G., Guicheux, J., Bonjour, J.-P., Caverzasio, J. (2000). Transforming Growth Factor-{beta} Stimulates Inorganic Phosphate Transport and Expression of the Type III Phosphate Transporter Glvr-1 in Chondrogenic ATDC5 Cells. Endocrinology 141: 2236-2243 [Abstract] [Full Text]
Liu, Y., Li, H., Tanaka, K., Tsumaki, N., Yamada, Y. (2000). Identification of an Enhancer Sequence within the First Intron Required for Cartilage-specific Transcription of the alpha 2(XI) Collagen Gene. J. Biol. Chem. 275: 12712-12718 [Abstract] [Full Text]
Kusanagi, K., Inoue, H., Ishidou, Y., Mishima, H. K., Kawabata, M., Miyazono, K. (2000). Characterization of a Bone Morphogenetic Protein-responsive Smad-binding Element. Mol. Biol. Cell 11: 555-565 [Abstract] [Full Text]
Thomas, D., Sunters, A, Gentry, A, Grigoriadis, A. (2000). Inhibition of chondrocyte differentiation in vitro by constitutive and inducible overexpression of the c-fos proto-oncogene. J. Cell Sci. 113: 439-450 [Abstract]
Akiyama, H., Hiraki, Y., Noda, M., Shigeno, C., Ito, H., Nakamura, T. (1999). Molecular Cloning and Biological Activity of a Novel Ha-Ras Suppressor Gene Predominantly Expressed in Skeletal Muscle, Heart, Brain, and Bone Marrow by Differential Display Using Clonal Mouse EC Cells, ATDC5. J. Biol. Chem. 274: 32192-32197 [Abstract] [Full Text]
Fujii, M., Takeda, K., Imamura, T., Aoki, H., Sampath, T. K., Enomoto, S., Kawabata, M., Kato, M., Ichijo, H., Miyazono, K. (1999). Roles of Bone Morphogenetic Protein Type I Receptors and Smad Proteins in Osteoblast and Chondroblast Differentiation. Mol. Biol. Cell 10: 3801-3813 [Abstract] [Full Text]
French, M.M., Smith, S.E., Akanbi, K., Sanford, T., Hecht, J., Farach-Carson, M.C., Carson, D.D. (1999). Expression of the Heparan Sulfate Proteoglycan, Perlecan, during Mouse Embryogenesis and Perlecan Chondrogenic Activity In Vitro. JCB 145: 1103-1115 [Abstract] [Full Text]
Ebisawa, T, Tada, K, Kitajima, I, Tojo, K, Sampath, T., Kawabata, M, Miyazono, K, Imamura, T (1999). Characterization of bone morphogenetic protein-6 signaling pathways in osteoblast differentiation. J. Cell Sci. 112: 3519-3527 [Abstract]
Fujishige, K., Yanaka, N., Akatsuka, H., Omori, K. (1998). Localization of clearance receptor in rat lung and trachea: association with chondrogenic differentiation. Am. J. Physiol. Lung Cell. Mol. Physiol. 274: L425-L431 [Abstract] [Full Text]
Stott, N., Chuong, C. (1997). Dual action of sonic hedgehog on chondrocyte hypertrophy: retrovirus mediated ectopic sonic hedgehog expression in limb bud micromass culture induces novel cartilage nodules that are positive for alkaline phosphatase and type X collagen. J. Cell Sci. 110: 2691-2701 [Abstract]
Shimizu, A., Tada, K., Shukunami, C., Hiraki, Y., Kurokawa, T., Magane, N., Kurokawa-Seo, M. (2001). A Novel Alternatively Spliced Fibroblast Growth Factor Receptor 3 Isoform Lacking the Acid Box Domain Is Expressed during Chondrogenic Differentiation of ATDC5 Cells. J. Biol. Chem. 276: 11031-11040 [Abstract] [Full Text]
Watanabe, H., de Caestecker, M. P., Yamada, Y. (2001). Transcriptional Cross-talk between Smad, ERK1/2, and p38 Mitogen-activated Protein Kinase Pathways Regulates Transforming Growth Factor-beta -induced Aggrecan Gene Expression in Chondrogenic ATDC5 Cells. J. Biol. Chem. 276: 14466-14473 [Abstract] [Full Text]
Negishi, Y., Ui, N., Nakajima, M., Kawashima, K., Maruyama, K., Takizawa, T., Endo, H. (2001). p21Cip-1/SDI-1/WAF-1 Gene Is Involved in Chondrogenic Differentiation of ATDC5 Cells in Vitro. J. Biol. Chem. 276: 33249-33256 [Abstract] [Full Text]