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Retinoids inhibit the differentiation of embryonic-mouse mesenchymal cells in vitro

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Summary

The influence of all-trans retinoic acid, 13-cis retinoid acic and two aromatic retinoids (Ro 10-1670, Ro 11-1430) on the chondrogenic differentiation of mesenchymal cells in vitro was studied electronmicroscopically. Organ cultures of limb buds from mouse embryos (Day 11) and high-density cultures of embryonic-mouse mesenchymal cells (Day 12) were used as experimental models. After a 6-day culture in the control medium, the development of hyaline cartilage was observed in both systems. In cultures which were treated with retinoids from Day 1 through Day 3 and then incubated in the control medium for 3 more days, the mesenchymal cells still maintained the morphological features of the blastema stage; cartilage synthesis was reduced (low retinoid concentrations) or completely absent (high retinoid concentrations). These findings indicate that the treatment of embryonic-mouse mesenchymal cells with retinoids induces a persistent and dose-dependent inhibition of chondrogenic differentiation, which in quantitative terms, is variably expressed during treatment with different retinoids. These inhibitory effects of retinoids on chondrogenesis are probably implicated in the pathogenetic mechanisms of their teratogenic action in vivo.

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References

  1. Bollag W (1981) From vitamin A to retinoids: chemical and pharmacological aspects. In: Orfanos CE, Braun-Falco O, Farber EM, Grupper C, Polano MK, Schuppli R (eds) Retinoids. Springer, Berlin Heidelberg New York, pp 5–11

    Google Scholar 

  2. Cairns JM (1977) Growth of normal and talpid chick wing buds. An experimental analysis. In: Ede DA, Hinchliffe JR, Balls M (eds) Vertebrate limb and somite morphogenesis. University Press, Cambridge, pp 123–137

    Google Scholar 

  3. Creek KE, Morre DJ (1980) Effects of retinol and retinol palmitate on glycolipid and glycoprotein galactosyltransferase activities of rat liver plasma membranes. Biochem Biophys Res Commun 95:1775–1780

    Google Scholar 

  4. Dahl IMS, Axelsson I (1980) The inhibition by retinoid acid of the biosynthesis of proteoglycans in corneal cell culture. Exp Eye Res 31:443–450

    Google Scholar 

  5. Dingle JT, Fell HB, Lucy JA (1966) Synthesis of connective tissue components. The effect of retinol and hydrocortisone on cultured limb bone rudiments. Biochem J 98:173–181

    Google Scholar 

  6. Elias PM, Williams ML (1981) Retinoids, cancer and the skin. Arch Dermatol 117:160–180

    Google Scholar 

  7. Geelen JAG, Peters PWJ (1979) Hypervitaminosis-A-induced teratogenesis. CRC Crit Rev Toxicol 6:351–357

    Google Scholar 

  8. Hassell JR, Pennypacker JP, Yamada KM, Pratt RM (1978) Changes in cell surface proteins during normal and vitamin-A-inhibited chondrogenesis in vitro. Ann NY Acad Sci 312:406–409

    Google Scholar 

  9. Kalter H, Warkany J (1961) Experimental production of congenital malformations in strains of inbred mouse by maternal treatment with hypervitaminosis A. Am J Phatol 38:1–21

    Google Scholar 

  10. Kelly RD, Fallon JF (1978) Identification and distribution of gap junctions in the mesoderm of developing chick limb buds. J Embryol Exp Morphol 46:99–110

    Google Scholar 

  11. Kistler A (1981) Teratogenesis of retinoic acid in rats: susceptible stages and suppression of retinoic-acid-induced limb malformations by cycloheximide. Teratology 23:25–31

    Google Scholar 

  12. Kochhar DM (1973) Limb development in mouse embryos. I. Analysis of teratogenic effects of retinoid acid. Teratology 1:289–298

    Google Scholar 

  13. Kubilus J, Rand R, Baden HP (1981) Effects of retinoic acid and other retinoids on the growth and differentiation of 3T3-supported human keratinocytes. In Vitro 17:789–795

    Google Scholar 

  14. Kwasigroch TE, Kochhar DM (1980) Vitamin A alters the internal viscosity of fragments of limb bud mesenchyme. J Embryol Exp Morphol 59:325–339

    Google Scholar 

  15. Lewis CA, Pratt RM, Pennypacker JP, Hassell JR (1978) Inhibition of limb chondrogenesis in vitro by vitamin A: alterations in cell surface characteristics. Dev Biol 64:31–47

    Google Scholar 

  16. Lotan R, Kramer RH, Neumann G, Lotan D, Nicolson GL (1980) Retinoic-acid-induced modifications in the growth and cell surface components of a human carcinoma (HeLa) cell line. Exp Cell Res 130:401–414

    Google Scholar 

  17. Maniglia CA, Sartorelli AC (1981) Retinoic-acid-induced alterations of glycosaminoglycan synthesis and deposition in B16F10 melanoma cells. Ann NY Acad Sci 359:322–330

    Google Scholar 

  18. Merker H-J, Krüger U, Zimmermann B (1981) Simulation of limb bud skeletogenesis in vitro. In: Neubert D, Merker H-J (eds) Culture techniques: 5th symposium on prenatal development. Walter de Gruyter, Berlin New York, pp 119–133

    Google Scholar 

  19. Neubert D, Merker H-J, Tapken S (1974) Comparative studies on the prenatal development of mouse extremities in vivo and in organ culture. Naunyn-Schmiedebergs Arch Pharmacol 286:251–270

    Google Scholar 

  20. Orfanos CE (1980) Oral retinoids: present status. Br J Dermatol 103:473–481

    Google Scholar 

  21. Pacifici M, Cossu G, Molinaro M, Tato F (1980) Vitamin A inhibits chondrogenesis but not myogenesis. Exp Cell Res 129:469–474

    Google Scholar 

  22. Sasak W, De Luca LM, Dion LD, Silverman-Jones CS (1980) Effect of retinoic acid on cell surface glycopeptides of cultured, spontaneously transformed mouse fibroblasts (BALB/C 3T12-3 cells). Cancer Res 40:1944–1949

    Google Scholar 

  23. Sauer GJR, Evans CA (1980) Hypervitaminosis A and matrix alterations in maxillary explants from 16-day rat embryos. Teratology 21:123–130

    Google Scholar 

  24. Searls RL, Hilfer SR, Mirow SW (1972) An ultrastructural study of early chondrogenesis in the chick wing bud. Dev Biol 28:123–137

    Google Scholar 

  25. Shapiro SS, Mott DJ (1981) Modulation of glycosaminoglycan biosynthesis by retinoids. Ann NY Acad Sci 359:306–321

    Google Scholar 

  26. Shapiro SS, Poon JP (1976) Effect of retinoic acid on chondrocyte glycosaminoglycan biosynthesis. Arch Biochem Biophys 174:74–81

    Google Scholar 

  27. Sporn MB, Newton DL (1981) Retinoids and chemoprevention of cancer. In: Zedeck MS, Lipkin M (eds) Inhibition of tumor induction and development. Plenum, New York London, pp 71–100

    Google Scholar 

  28. Summerbell D (1976) A descriptive study of the rate of elongation and differentiation of the skeleton of the developing chick wing. J Embryol Exp Morphol 35:241–260

    Google Scholar 

  29. Taylor IM, Wiley MJ, Agur A (1980) Retinoic-acid-induced heart malformations in the hamster. Teratology 21:193–197

    Google Scholar 

  30. Trowell OA (1959) The culture of mature organs in a synthetic medium. Exp Cell Res 16:118–147

    Google Scholar 

  31. Tsambaos D, Orfanos CE (1981) Chemotherapy of psoriasis and other skin disorders with oral retinoids. Pharmacol Ther 14:355–374

    Google Scholar 

  32. Vasan NS (1981) Proteoglycan synthesis by sternal chondrocytes perturbed with vitamin A. J Embryol Exp Morphol 63:181–191

    Google Scholar 

  33. Vasan NS, Lash JW (1975) Chondrocyte metabolism as affected by vitamin A. Calcif Tissue Int 19:99–107

    Google Scholar 

  34. Zimmermann B (1981) Cell movement during blastema formation. Effect of cytochalasin B on cartilage development in vitro. In: Neubert D, Merker H-J (eds) Culture techniques: 5th symposium on prenatal development. Walter de Gruyter, Berlin New York, pp 465–475

    Google Scholar 

  35. Zimmermann B, Scharlach E, Kaatz R (1982) Cell contact and surface coat alterations of limb bud mesenchymal cells during differentiation. J Embryol Exp Morphol 72:1–18

    Google Scholar 

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Authors and Affiliations

  1. Institute of Toxicology and Prenatal Pharmacology, University Medical Centre Steglitz, The Free University of Berlin, D-1000, Berlin

    B. Zimmermann

  2. Department of Dermatology, University Medical Centre Steglitz, The Free University of Berlin, D-1000, Berlin

    D. Tsambaos

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  1. B. Zimmermann
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Zimmermann, B., Tsambaos, D. Retinoids inhibit the differentiation of embryonic-mouse mesenchymal cells in vitro. Arch Dermatol Res 277, 98–104 (1985). https://doi.org/10.1007/BF00414105

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  • DOI: https://doi.org/10.1007/BF00414105

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