Endocrinology, Vol 107, 1494-1503, Copyright © 1980 by Endocrine Society

ARTICLES

Parathyroid hormone-responsive clonal cell lines from rat osteosarcoma

RJ Majeska, SB Rodan and GA Rodan

Several clonal cell lines from a transplantable rat osteosarcoma, selected on the basis of parathyroid hormone (PTH)-sensitive adenylate cyclase, were established in culture. Bovine PTH-(1-84) (0.1 microM) stimulation of adenylate cyclase varied among clones from 8-fold to none. The level of PTH response was a stable property of each clonal line that was retained through numerous passages in vitro (nearly 3 yr in the oldest clone). Highly PTH-responsive lines had a cuboidal- eliptoid morphology and differed from the nonresponsive lines, which had a more fibroblastic appearance. PTH responsiveness correlated with several properties, presumably associated with the osteoblastic phenotype: elevated alkaline phosphatase activity, synthesis of the gamma-carboxyglutamic acid-containing bone protein, and production of mineralized tumors in host rats. PTH (1.0 nM; 24 h) reduced the alkaline phosphatase activity by 40% when tested in a responsive clone. The acid phosphatase activity of the various cell lines was uniformly low. These osteosarcoma-derived cell lines which are stable in vitro thus seem to reflect the phenotypic heterogeneity observed in the tumor in situ. They could be useful in studies of phenotypic expression, PTH action, and a possible relationship between the two.

This article has been cited by other articles:

				T. Dean, J.-P. Vilardaga, J. T. Potts Jr., and T. J. Gardella Altered Selectivity of Parathyroid Hormone (PTH) and PTH-Related Protein (PTHrP) for Distinct Conformations of the PTH/PTHrP Receptor Mol. Endocrinol., January 1, 2008; 22(1): 156 - 166. [Abstract] [Full Text] [PDF]

				A. Villagra, F. Cruzat, L. Carvallo, R. Paredes, J. Olate, A. J. van Wijnen, G. S. Stein, J. B. Lian, J. L. Stein, A. N. Imbalzano, et al. Chromatin Remodeling and Transcriptional Activity of the Bone-specific Osteocalcin Gene Require CCAAT/Enhancer-binding Protein beta-dependent Recruitment of SWI/SNF Activity J. Biol. Chem., August 11, 2006; 281(32): 22695 - 22706. [Abstract] [Full Text] [PDF]

				V. W.C. Yu, G. Ambartsoumian, L. Verlinden, J. M. Moir, J. Prud'homme, C. Gauthier, P. J. Roughley, and R. St-Arnaud FIAT represses ATF4-mediated transcription to regulate bone mass in transgenic mice J. Cell Biol., May 23, 2005; 169(4): 591 - 601. [Abstract] [Full Text] [PDF]

				X. Chen, J.-C. Dai, S. A. Orellana, and E. M. Greenfield Endogenous Protein Kinase Inhibitor {gamma} Terminates Immediate-early Gene Expression Induced by cAMP-dependent Protein Kinase (PKA) Signaling: TERMINATION DEPENDS ON PKA INACTIVATION RATHER THAN PKA EXPORT FROM THE NUCLEUS J. Biol. Chem., January 28, 2005; 280(4): 2700 - 2707. [Abstract] [Full Text] [PDF]

				R. Paredes, G. Arriagada, F. Cruzat, A. Villagra, J. Olate, K. Zaidi, A. van Wijnen, J. B. Lian, G. S. Stein, J. L. Stein, et al. Bone-Specific Transcription Factor Runx2 Interacts with the 1{alpha},25-Dihydroxyvitamin D3 Receptor To Up-Regulate Rat Osteocalcin Gene Expression in Osteoblastic Cells Mol. Cell. Biol., October 15, 2004; 24(20): 8847 - 8861. [Abstract] [Full Text] [PDF]

				N. Boutahar, A. Guignandon, L. Vico, and M.-H. Lafage-Proust Mechanical Strain on Osteoblasts Activates Autophosphorylation of Focal Adhesion Kinase and Proline-rich Tyrosine Kinase 2 Tyrosine Sites Involved in ERK Activation J. Biol. Chem., July 16, 2004; 279(29): 30588 - 30599. [Abstract] [Full Text] [PDF]

				J. Sierra, A. Villagra, R. Paredes, F. Cruzat, S. Gutierrez, A. Javed, G. Arriagada, J. Olate, M. Imschenetzky, A. J. van Wijnen, et al. Regulation of the Bone-Specific Osteocalcin Gene by p300 Requires Runx2/Cbfa1 and the Vitamin D3 Receptor but Not p300 Intrinsic Histone Acetyltransferase Activity Mol. Cell. Biol., May 1, 2003; 23(9): 3339 - 3351. [Abstract] [Full Text] [PDF]

				X. Chen, J.-C. Dai, and E. M. Greenfield Termination of immediate-early gene expression after stimulation by parathyroid hormone or isoproterenol Am J Physiol Cell Physiol, November 1, 2002; 283(5): C1432 - C1440. [Abstract] [Full Text] [PDF]

				A. Zambotti, H. Makhluf, J. Shen, and P. Ducy Characterization of an Osteoblast-specific Enhancer Element in the CBFA1 Gene J. Biol. Chem., October 25, 2002; 277(44): 41497 - 41506. [Abstract] [Full Text] [PDF]

				G. Xiao, D. Jiang, R. Gopalakrishnan, and R. T. Franceschi Fibroblast Growth Factor 2 Induction of the Osteocalcin Gene Requires MAPK Activity and Phosphorylation of the Osteoblast Transcription Factor, Cbfa1/Runx2 J. Biol. Chem., September 20, 2002; 277(39): 36181 - 36187. [Abstract] [Full Text] [PDF]

				K. Sooy and M. B. Demay Transcriptional Repression of the Rat Osteocalcin Gene by {delta}EF1 Endocrinology, September 1, 2002; 143(9): 3370 - 3375. [Abstract] [Full Text] [PDF]

				J. Shen, M. Montecino, J. B. Lian, G. S. Stein, A. J. van Wijnen, and J. L. Stein Histone Acetylation in Vivo at the Osteocalcin Locus Is Functionally Linked to Vitamin D-dependent, Bone Tissue-specific Transcription J. Biol. Chem., May 31, 2002; 277(23): 20284 - 20292. [Abstract] [Full Text] [PDF]

				M. E. Nuttall, G. B. Stroup, P. W. Fisher, D. P. Nadeau, M. Gowen, and L. J. Suva Distinct mechanisms of action of selective estrogen receptor modulators in breast and osteoblastic cells Am J Physiol Cell Physiol, November 1, 2000; 279(5): C1550 - C1557. [Abstract] [Full Text] [PDF]

				M. D. Benson, J. L. Bargeon, G. Xiao, P. E. Thomas, A. Kim, Y. Cui, and R. T. Franceschi Identification of a Homeodomain Binding Element in the Bone Sialoprotein Gene Promoter That Is Required for Its Osteoblast-selective Expression J. Biol. Chem., April 28, 2000; 275(18): 13907 - 13917. [Abstract] [Full Text] [PDF]

				I. Sekiya, K. Tsuji, P. Koopman, H. Watanabe, Y. Yamada, K. Shinomiya, A. Nifuji, and M. Noda SOX9 Enhances Aggrecan Gene Promoter/Enhancer Activity and Is Up-regulated by Retinoic Acid in a Cartilage-derived Cell Line, TC6 J. Biol. Chem., April 6, 2000; 275(15): 10738 - 10744. [Abstract] [Full Text] [PDF]

				P. W. Jurutka, L. S. Remus, G. K. Whitfield, P. D. Thompson, J.-C. Hsieh, H. Zitzer, P. Tavakkoli, M. A. Galligan, H. T. L. Dang, C. A. Haussler, et al. The Polymorphic N Terminus in Human Vitamin D Receptor Isoforms Influences Transcriptional Activity by Modulating Interaction with Transcription Factor IIB Mol. Endocrinol., March 1, 2000; 14(3): 401 - 420. [Abstract] [Full Text]

				G. Xiao, D. Jiang, P. Thomas, M. D. Benson, K. Guan, G. Karsenty, and R. T. Franceschi MAPK Pathways Activate and Phosphorylate the Osteoblast-specific Transcription Factor, Cbfa1 J. Biol. Chem., February 11, 2000; 275(6): 4453 - 4459. [Abstract] [Full Text] [PDF]

				S. E. Hahn, M. Yu, S. Tong, A. A.T. Geisterfer-Lowrance, D. Sindrey, and D. K.H. Lee Development of an In Vitro Screening Assay for Compounds that Increase Bone Formation J Biomol Screen, December 1, 1999; 4(6): 363 - 371. [Abstract] [PDF]

				K. M. Dougherty, E. A. G. Blomme, A. J. Koh, J. E. Henderson, K. J. Pienta, T. J. Rosol, and L. K. McCauley Parathyroid Hormone-related Protein as a Growth Regulator of Prostate Carcinoma Cancer Res., December 1, 1999; 59(23): 6015 - 6022. [Abstract] [Full Text] [PDF]

				H. Drissi, D. Hushka, F. Aslam, Q. Nguyen, E. Buffone, A. Koff, A. J. van Wijnen, J. B. Lian, J. L. Stein, and G. S. Stein The Cell Cycle Regulator p27kip1 Contributes to Growth and Differentiation of Osteoblasts Cancer Res., August 1, 1999; 59(15): 3705 - 3711. [Abstract] [Full Text] [PDF]

				I. Bab, E. Smith, H. Gavish, M. Attar-Namdar, M. Chorev, Y.-C. Chen, A. Muhlrad, M. J. Birnbaum, G. Stein, and B. Frenkel Biosynthesis of Osteogenic Growth Peptide via Alternative Translational Initiation at AUG85 of Histone H4 mRNA J. Biol. Chem., May 14, 1999; 274(20): 14474 - 14481. [Abstract] [Full Text] [PDF]

				M. E. Nuttall, J. N. Bradbeer, G. B. Stroup, D. P. Nadeau, S. J. Hoffman, H. Zhao, S. Rehm, and M. Gowen Idoxifene: A Novel Selective Estrogen Receptor Modulator Prevents Bone Loss and Lowers Cholesterol Levels in Ovariectomized Rats and Decreases Uterine Weight in Intact Rats Endocrinology, December 1, 1998; 139(12): 5224 - 5234. [Abstract] [Full Text] [PDF]

				F. Lecanda, D. A. Towler, K. Ziambaras, S.-L. Cheng, M. Koval, T. H. Steinberg, and R. Civitelli Gap Junctional Communication Modulates Gene Expression in Osteoblastic Cells Mol. Biol. Cell, August 1, 1998; 9(8): 2249 - 2258. [Abstract] [Full Text]

				Y. Taketani, H. Segawa, M. Chikamori, K. Morita, K. Tanaka, S. Kido, H. Yamamoto, Y. Iemori, S. Tatsumi, N. Tsugawa, et al. Regulation of Type II Renal Na+-dependent Inorganic Phosphate Transporters by 1,25-Dihydroxyvitamin D3. IDENTIFICATION OF A VITAMIN D-RESPONSIVE ELEMENT IN THE HUMAN NAPI-3 GENE J. Biol. Chem., June 5, 1998; 273(23): 14575 - 14581. [Abstract] [Full Text] [PDF]

				A. Moreau, W. V. Yotov, F. H. Glorieux, and R. St-Arnaud Bone-Specific Expression of the Alpha Chain of the Nascent Polypeptide-Associated Complex, a Coactivator Potentiating c-Jun-Mediated Transcription Mol. Cell. Biol., March 1, 1998; 18(3): 1312 - 1321. [Abstract] [Full Text]

				F. J. Dilworth, G. R. Williams, A.-M. Kissmeyer, J. L. Nielsen, E. Binderup, M. J. Calverley, H. L. J. Makin, and G. Jones The Vitamin D Analog, KH1060, Is Rapidly Degraded Both in Vivo and in Vitro via Several Pathways: Principal Metabolites Generated Retain Significant Biological Activity Endocrinology, December 1, 1997; 138(12): 5485 - 5496. [Abstract] [Full Text] [PDF]

				Y. Ezura, O. Tournay, A. Nifuji, and M. Noda Identification of a Novel Suppressive Vitamin D Response Sequence in the 5'-Flanking Region of the Murine Id1 Gene J. Biol. Chem., November 21, 1997; 272(47): 29865 - 29872. [Abstract] [Full Text] [PDF]

				H. M. Ryoo, H. M. Hoffmann, T. Beumer, B. Frenkel, D. A. Towler, G. S. Stein, J. L. Stein, A. J. van Wijnen, and J. B. Lian Stage-Specific Expression of Dlx-5 during Osteoblast Differentiation: Involvement in Regulation of Osteocalcin Gene Expression Mol. Endocrinol., October 1, 1997; 11(11): 1681 - 1694. [Abstract] [Full Text]

				S. Murakami, A. Nifuji, and M. Noda Expression of Indian Hedgehog in Osteoblasts and Its Posttranscriptional Regulation by Transforming Growth Factor-{beta} Endocrinology, May 1, 1997; 138(5): 1972 - 1978. [Abstract] [Full Text] [PDF]

				B. Guo, F. Aslam, A. J. van Wijnen, S. G. E. Roberts, B. Frenkel, M. R. Green, H. DeLuca, J. B. Lian, G. S. Stein, and J. L. Stein YY1 regulates vitamin D receptor/retinoid X receptor mediated transactivation of the vitamin D responsive osteocalcin gene PNAS, January 7, 1997; 94(1): 121 - 126. [Abstract] [Full Text] [PDF]

				R. Zhang, P. Ducy, and G. Karsenty 1,25-Dihydroxyvitamin D3 Inhibits Osteocalcin Expression in Mouse through an Indirect Mechanism J. Biol. Chem., January 3, 1997; 272(1): 110 - 116. [Abstract] [Full Text] [PDF]

				M. A. V. Molen, C. T. Rubin, K. J. McLeod, L. K. McCauley, and H. J. Donahue Gap Junctional Intercellular Communication Contributes to Hormonal Responsiveness in Osteoblastic Networks J. Biol. Chem., May 24, 1996; 271(21): 12165 - 12171. [Abstract] [Full Text] [PDF]

				J. M. Boudreaux and D. A. Towler Synergistic Induction of Osteocalcin Gene Expression J. Biol. Chem., March 29, 1996; 271(13): 7508 - 7515. [Abstract] [Full Text] [PDF]

				S Kellokumpu, L Neff, S Jamsa-Kellokumpu, R Kopito, and R Baron A 115-kD polypeptide immunologically related to erythrocyte band 3 is present in Golgi membranes Science, December 2, 1988; 242(4883): 1308 - 1311. [Abstract] [PDF]

				J. Merendino Jr, K. Insogna, L. Milstone, A. Broadus, and A. Stewart A parathyroid hormone-like protein from cultured human keratinocytes Science, January 24, 1986; 231(4736): 388 - 390. [Abstract] [PDF]

				E. Shimizu-Sasaki, M. Yamazaki, S. Furuyama, H. Sugiya, J. Sodek, and Y. Ogata Identification of a Novel Response Element in the Rat Bone Sialoprotein (BSP) Gene Promoter that Mediates Constitutive and Fibroblast Growth Factor 2-induced Expression of BSP J. Biol. Chem., February 16, 2001; 276(8): 5459 - 5466. [Abstract] [Full Text] [PDF]

				M. Shimizu, J. T. Potts Jr., and T. J. Gardella Minimization of Parathyroid Hormone. NOVEL AMINO-TERMINAL PARATHYROID HORMONE FRAGMENTS WITH ENHANCED POTENCY IN ACTIVATING THE TYPE-1 PARATHYROID HORMONE RECEPTOR J. Biol. Chem., July 14, 2000; 275(29): 21836 - 21843. [Abstract] [Full Text] [PDF]