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. 1990 Mar;85(3):626–631. doi: 10.1172/JCI114484

Potent mitogenic effects of parathyroid hormone (PTH) on embryonic chick and rabbit chondrocytes. Differential effects of age on growth, proteoglycan, and cyclic AMP responses of chondrocytes to PTH.

T Koike 1, M Iwamoto 1, A Shimazu 1, K Nakashima 1, F Suzuki 1, Y Kato 1
PMCID: PMC296475  PMID: 2155920

Abstract

The effect of PTH on chondrocyte proliferation as a function of cartilage age was examined. PTH[1-34] induced a 12- to 15-fold increase in the efficiency of colony formation in soft agar by chondrocytes from embryonic 13- to 19-d-old chickens and fetal 25-d-old rabbits with a 10-fold increase in their DNA content. It also caused a 2.5-fold increase in [3H]thymidine incorporation into DNA in fetal 25-d-old rabbit chondrocytes. No mitogenic responses to PTH were observed, however, in postnatal 7- to 21-d-old chick chondrocytes or postnatal 21-d-old rabbit chondrocytes. This age dependency was observed only with PTH: fibroblast growth factor, epidermal growth factor, and insulin stimulated chondrocyte proliferation irrespective of cartilage age. The absence of a mitogenic effect in postnatal chondrocytes was not due to a decrease in number or a reduction in affinity of receptors for PTH. PTH also increased [35S]sulfate incorporation into proteoglycans and the cyclic AMP level in fetal and postnatal chondrocytes, but at 100-fold higher concentrations (10(-8)-10(-7) M) than those (10(-10)-10(-9) M) required for the stimulation of cell division. These results suggest that PTH is a potent mitogen for embryonic chondrocytes, and that its mitogenic effect disappears selectively after birth.

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Selected References

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  1. Benya P. D., Shaffer J. D. Dedifferentiated chondrocytes reexpress the differentiated collagen phenotype when cultured in agarose gels. Cell. 1982 Aug;30(1):215–224. doi: 10.1016/0092-8674(82)90027-7. [DOI] [PubMed] [Google Scholar]
  2. Bomboy J. D., Jr, Salmon W. D., Jr Effects of cyclic nucleotides on deoxyribonucleic acid synthesis in hypophysectomized rat cartilage: stimulation of thymidine incorporation and potentiation of the action of somatomedin by analogs of adenosine 3',5'-monophosphate or a cyclic nucleotide phosphodiesterase inhibitor. Endocrinology. 1980 Aug;107(2):626–632. doi: 10.1210/endo-107-2-626. [DOI] [PubMed] [Google Scholar]
  3. Burch W. M., Lebovitz H. E. Parathyroid hormone stimulates growth of embryonic chick pelvic cartilage in vitro. Calcif Tissue Int. 1983 Jul;35(4-5):526–532. doi: 10.1007/BF02405088. [DOI] [PubMed] [Google Scholar]
  4. Burch W. M., Weir S., Van Wyk J. J. Embryonic chick cartilage produces its own somatomedin-like peptide to stimulate cartilage growth in vitro. Endocrinology. 1986 Sep;119(3):1370–1376. doi: 10.1210/endo-119-3-1370. [DOI] [PubMed] [Google Scholar]
  5. Canalis E., Centrella M., Burch W., McCarthy T. L. Insulin-like growth factor I mediates selective anabolic effects of parathyroid hormone in bone cultures. J Clin Invest. 1989 Jan;83(1):60–65. doi: 10.1172/JCI113885. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Care A. D., Caple I. W., Singh R., Peddie M. Studies on calcium homeostasis in the fetal Yucatan miniature pig. Lab Anim Sci. 1986 Aug;36(4):389–392. [PubMed] [Google Scholar]
  7. Carrington J. L., Roberts A. B., Flanders K. C., Roche N. S., Reddi A. H. Accumulation, localization, and compartmentation of transforming growth factor beta during endochondral bone development. J Cell Biol. 1988 Nov;107(5):1969–1975. doi: 10.1083/jcb.107.5.1969. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Drezner M. K., Neelon F. A., Lebovitz H. E. Stimulation of cartilage macromolecule synthesis by adenosine 3',5'-monophosphate. Biochim Biophys Acta. 1976 Apr 2;425(4):521–531. doi: 10.1016/0005-2787(76)90016-2. [DOI] [PubMed] [Google Scholar]
  9. Goldring S. R., Tyler G. A., Krane S. M., Potts J. T., Jr, Rosenblatt M. Photoaffinity labeling of parathyroid hormone receptors: comparison of receptors across species and target tissues and after desensitization to hormone. Biochemistry. 1984 Jan 31;23(3):498–502. doi: 10.1021/bi00298a015. [DOI] [PubMed] [Google Scholar]
  10. Hinegardner R. T. An improved fluorometric assay for DNA. Anal Biochem. 1971 Jan;39(1):197–201. doi: 10.1016/0003-2697(71)90476-3. [DOI] [PubMed] [Google Scholar]
  11. Hiraki Y., Yutani Y., Takigawa M., Kato Y., Suzuki F. Differential effects of parathyroid hormone and somatomedin-like growth factors on the sizes of proteoglycan monomers and their synthesis in rabbit costal chondrocytes in culture. Biochim Biophys Acta. 1985 Jun 30;845(3):445–453. doi: 10.1016/0167-4889(85)90210-1. [DOI] [PubMed] [Google Scholar]
  12. Honma M., Satoh T., Takezawa J., Ui M. An ultrasensitive method for the simultaneous determination of cyclic AMP and cyclic GMP in small-volume samples from blood and tissue. Biochem Med. 1977 Dec;18(3):257–273. doi: 10.1016/0006-2944(77)90060-6. [DOI] [PubMed] [Google Scholar]
  13. Iwamoto M., Sato K., Nakashima K., Fuchihata H., Suzuki F., Kato Y. Regulation of colony formation of differentiated chondrocytes in soft agar by transforming growth factor-beta. Biochem Biophys Res Commun. 1989 Mar 31;159(3):1006–1011. doi: 10.1016/0006-291x(89)92208-0. [DOI] [PubMed] [Google Scholar]
  14. Kato Y., Gospodarowicz D. Sulfated proteoglycan synthesis by confluent cultures of rabbit costal chondrocytes grown in the presence of fibroblast growth factor. J Cell Biol. 1985 Feb;100(2):477–485. doi: 10.1083/jcb.100.2.477. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kato Y., Iwamoto M., Koike T. Fibroblast growth factor stimulates colony formation of differentiated chondrocytes in soft agar. J Cell Physiol. 1987 Dec;133(3):491–498. doi: 10.1002/jcp.1041330309. [DOI] [PubMed] [Google Scholar]
  16. Kato Y., Iwamoto M., Koike T., Suzuki F., Takano Y. Terminal differentiation and calcification in rabbit chondrocyte cultures grown in centrifuge tubes: regulation by transforming growth factor beta and serum factors. Proc Natl Acad Sci U S A. 1988 Dec;85(24):9552–9556. doi: 10.1073/pnas.85.24.9552. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Kato Y., Koike T., Iwamoto M., Kinoshita M., Sato K., Hiraki Y., Suzuki F. Effects of limited exposure of rabbit chondrocyte cultures to parathyroid hormone and dibutyryl adenosine 3',5'-monophosphate on cartilage-characteristic proteoglycan synthesis. Endocrinology. 1988 May;122(5):1991–1997. doi: 10.1210/endo-122-5-1991. [DOI] [PubMed] [Google Scholar]
  18. Kato Y., Nomura Y., Daikuhara Y., Nasu N., Tsuji M., Asada A., Suzuki F. Cartilage-derived factor (CDF) I. Stimulation of proteoglycan synthesis in rat and rabbit costal chondrocytes in culture. Exp Cell Res. 1980 Nov;130(1):73–81. doi: 10.1016/0014-4827(80)90043-9. [DOI] [PubMed] [Google Scholar]
  19. Kato Y., Nomura Y., Tsuji M., Ohmae H., Kinoshita M., Hamamoto S., Suzuki F. Cartilage-derived factor (CDF). II. Somatomedin-like action on cultured chondrocytes. Exp Cell Res. 1981 Apr;132(2):339–347. doi: 10.1016/0014-4827(81)90109-9. [DOI] [PubMed] [Google Scholar]
  20. Kawashima K., Iwata S., Endo H. Growth stimulative effect of parathyroid hormone, calcitonin and N6,O2'-dibutyryl adenosine 3';5'-cyclic monophosphoric acid on chick embryonic cartilage cultivated in a chemically defined medium. Endocrinol Jpn. 1980 Jun;27(3):349–356. doi: 10.1507/endocrj1954.27.349. [DOI] [PubMed] [Google Scholar]
  21. Kinoshita M., Kato Y., Tsuji M., Kono T., Hiraki Y., Suzuki F. Prostaglandin stimulation of adenosine 3',5'-monophosphate accumulation in cultured chondrocytes in the presence or absence of parathyroid hormone. Biochim Biophys Acta. 1983 Jun 9;757(3):324–331. doi: 10.1016/0304-4165(83)90058-2. [DOI] [PubMed] [Google Scholar]
  22. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  23. Lewinson D., Silbermann M. Parathyroid hormone stimulates proliferation of chondroprogenitor cells in vitro. Calcif Tissue Int. 1986 Mar;38(3):155–162. doi: 10.1007/BF02556875. [DOI] [PubMed] [Google Scholar]
  24. Nilsson A., Isgaard J., Lindahl A., Dahlström A., Skottner A., Isaksson O. G. Regulation by growth hormone of number of chondrocytes containing IGF-I in rat growth plate. Science. 1986 Aug 1;233(4763):571–574. doi: 10.1126/science.3523759. [DOI] [PubMed] [Google Scholar]
  25. Northrop G., Misenhimer H. R., Becker F. O. Failure of parathyroid hormone to cross the nonhuman primate placenta. Am J Obstet Gynecol. 1977 Oct 15;129(4):449–453. doi: 10.1016/0002-9378(77)90593-2. [DOI] [PubMed] [Google Scholar]
  26. Pitkin R. M., Reynolds W. A., Williams G. A., Kawahara W., Bauman A. F., Hargis G. K. Maternal and fetal parathyroid hormone responsiveness in pregnant primates. J Clin Endocrinol Metab. 1980 Nov;51(5):1044–1047. doi: 10.1210/jcem-51-5-1044. [DOI] [PubMed] [Google Scholar]
  27. SCOTHORNE R. J. FUNCTIONAL CAPACITY OF FETAL PARATHYROID GLANDS WITH REFERENCE TO THEIR CLINICAL USE AS HOMOGRAFTS. Ann N Y Acad Sci. 1964 Nov 30;120:669–676. doi: 10.1111/j.1749-6632.1964.tb34761.x. [DOI] [PubMed] [Google Scholar]
  28. Shigeno C., Hiraki Y., Westerberg D. P., Potts J. T., Jr, Segre G. V. Photoaffinity labeling of parathyroid hormone receptors in clonal rat osteosarcoma cells. J Biol Chem. 1988 Mar 15;263(8):3864–3871. [PubMed] [Google Scholar]
  29. Shimomura Y., Yoneda T., Suzuki F. Osteogenesis by chondrocytes from growth cartilage of rat rib. Calcif Tissue Res. 1975 Dec 22;19(3):179–187. doi: 10.1007/BF02564002. [DOI] [PubMed] [Google Scholar]
  30. Suzuki F., Yoneda T., Shimomura Y. Calcitonin and parathyroid-hormone stimulation of acid mucopolysaccharide synthesis in cultured chondrocytes isolated from growth cartilage. FEBS Lett. 1976 Nov;70(1):155–158. doi: 10.1016/0014-5793(76)80747-8. [DOI] [PubMed] [Google Scholar]
  31. Takano T., Takigawa M., Suzuki F. Role of polyamines in expression of the differentiated phenotype of chondrocytes: effect of DL-alpha-hydrazino-delta-aminovaleric acid (DL-HAVA), an inhibitor of ornithine decarboxylase, on chondrocytes treated with parathyroid hormone. J Biochem. 1983 Feb;93(2):591–598. doi: 10.1093/oxfordjournals.jbchem.a134214. [DOI] [PubMed] [Google Scholar]
  32. Takigawa M., Takano T., Suzuki F. Effects of parathyroid hormone and cyclic AMP analogues on the activity of ornithine decarboxylase and expression of the differentiated phenotype of chondrocytes in culture. J Cell Physiol. 1981 Feb;106(2):259–268. doi: 10.1002/jcp.1041060212. [DOI] [PubMed] [Google Scholar]

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