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. 1961 Jan 31;113(2):381–403. doi: 10.1084/jem.113.2.381

METABOLIC EFFECTS OF LATHYROGENIC AGENTS ON CARTILAGE IN VIVO AND IN VITRO

Morris J Karnovsky 1, Manfred L Karnovsky 1
PMCID: PMC2137357  PMID: 13751545

Abstract

The effects of lathyrogenic agents in vivo and in vitro are described, in respect to some biochemical indices of cartilage metabolism. Lathyrogenic agents in vivo inhibited the incorporation of radiosulfate into rat epiphyseal cartilage and the isolated chondroitin sulfate. No significant changes in hydroxyproline or hexosamine content of epiphyseal cartilage were found, but there was a marked increase in water content. The content of chondroitin sulfate, measured as uronic acid, was decreased. The importance of taking growth rate differences between control and experimental rats into account in assessing the effects of lathyrogenic agents in vivo is emphasized. In an in vitro system, utilizing fresh calf costal cartilage slices, the presence of low concentrations of lathyrogenic agents markedly affected various metabolic events. The incorporation into cartilage slices of sulfate-S35, glucose-U-C14, and glycine-1-C14 was significantly depressed, as was the production of organic acids, including lactic acid. In general, these effects were more severe under anaerobic conditions. Glutamine restored the activities of the slices treated with lathyrogenic agents to control values obtained in the absence of either lathyrogen or glutamine.

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Selected References

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  1. BAUER G. C., CARLSSON A., LINDQUIST B. Skeletal uptake of sulfate and phosphate in beta-aminopropiononitrile poisoned rats. Acta Pathol Microbiol Scand. 1955;37(5):407–413. doi: 10.1111/j.1699-0463.1955.tb00963.x. [DOI] [PubMed] [Google Scholar]
  2. BEAN W. B., PONSETI I. V. Dissecting aneurysm produced by diet. Circulation. 1955 Aug;12(2):185–192. doi: 10.1161/01.cir.12.2.185. [DOI] [PubMed] [Google Scholar]
  3. BOAS N. F. Method for the determination of hexosamines in tissues. J Biol Chem. 1953 Oct;204(2):553–563. [PubMed] [Google Scholar]
  4. BORLE A. B., KARNOVSKY M. J., NICHOLS G., Jr Changes in inorganic composition of tissues in experimental osteolathyrism. Am J Physiol. 1959 Dec;197:1224–1228. doi: 10.1152/ajplegacy.1959.197.6.1224. [DOI] [PubMed] [Google Scholar]
  5. BOYD E. S., NEUMAN W. F. Chondroitin sulfate synthesis and respiration in chick embryonic cartilage. Arch Biochem Biophys. 1954 Aug;51(2):475–486. doi: 10.1016/0003-9861(54)90503-2. [DOI] [PubMed] [Google Scholar]
  6. BRUEMMER N. C., LALICH J. J., MUELLER G. C. Effect of beta-aminopropionitrile on incorporation of glycine by croton oil pouches in rats. Proc Soc Exp Biol Med. 1957 Nov;96(2):340–345. doi: 10.3181/00379727-96-23472. [DOI] [PubMed] [Google Scholar]
  7. CASTELLANI A. A., CASTELLANI-BISI C. Decrease in hexosamine content of epiphyseal plates in experimental lathyrism. Proc Soc Exp Biol Med. 1958 Jun;98(2):318–320. doi: 10.3181/00379727-98-24030. [DOI] [PubMed] [Google Scholar]
  8. DASLER W. Production of experimental lathyrism in the rat by two different beta-substituted ethylamines. Proc Soc Exp Biol Med. 1955 Feb;88(2):196–199. doi: 10.3181/00379727-88-21535. [DOI] [PubMed] [Google Scholar]
  9. DASLER W. Protective action of glutamine, cysteine and other substances against experimental lathyrism in the rat. Proc Soc Exp Biol Med. 1956 Apr;91(4):554–557. doi: 10.3181/00379727-91-22325. [DOI] [PubMed] [Google Scholar]
  10. ENGFELDT B., WESTERBORN O. An autoradiographic study of the epiphyseal cartilage in normal rabbits after administration of radiosulphate. Acta Pathol Microbiol Scand. 1960;49:73–81. doi: 10.1111/j.1699-0463.1960.tb01115.x. [DOI] [PubMed] [Google Scholar]
  11. FOLLIS R. H., Jr, TOUSIMIS A. J. Experimental lathyrism in the rat; nature of defect in epiphysial cartilage. Proc Soc Exp Biol Med. 1958 Aug-Sep;98(4):843–848. doi: 10.3181/00379727-98-24204. [DOI] [PubMed] [Google Scholar]
  12. GARDNER A. F., DASLER W., WEINMANN J. P. Masticatory apparatus of albino rats in experimental lathyrism. J Dent Res. 1958 Jun;37(3):492–515. doi: 10.1177/00220345580370032201. [DOI] [PubMed] [Google Scholar]
  13. GILLMAN T., HATHORN M. Rates of growth and of remodelling as factors in the genesis of vascular and osseous lesions of odoratism in rats. J Embryol Exp Morphol. 1958 Jun;6(2):270–283. [PubMed] [Google Scholar]
  14. GRANT R. A., HATHORN M., GILLMAN T. Aortic, serum, connective tissue and osseous chemistry in lathyritic rats. Nature. 1960 Apr 9;186:164–165. doi: 10.1038/186164a0. [DOI] [PubMed] [Google Scholar]
  15. Gross J., Highberger J. H., Schmitt F. O. EXTRACTION OF COLLAGEN FROM CONNECTIVE TISSUE BY NEUTRAL SALT SOLUTIONS. Proc Natl Acad Sci U S A. 1955 Jan 15;41(1):1–7. doi: 10.1073/pnas.41.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. HIGHBERGER J. H., GROSS J., SCHMITT F. O. The interaction of mucoprotein with soluble collagen; an electron microscope study. Proc Natl Acad Sci U S A. 1951 May;37(5):286–291. doi: 10.1073/pnas.37.5.286. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. JACKSON D. S. Chondroitin sulphuric acid as a factor in the stability of tendon. Biochem J. 1953 Jul;54(4):638–641. doi: 10.1042/bj0540638. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. JACKSON D. S. The nature of collagen-chondroitin sulphate linkages in tendon. Biochem J. 1954 Apr;56(4):699–703. doi: 10.1042/bj0560699. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. KAPLAN D., MEYER K. Ageing of human cartilage. Nature. 1959 May 2;183(4670):1267–1268. doi: 10.1038/1831267a0. [DOI] [PubMed] [Google Scholar]
  20. KARNOVSKY M. J. Effect of lathyrogenic agents on glycogen in epiphyseal cartilage. Lab Invest. 1960 Nov-Dec;9:639–655. [PubMed] [Google Scholar]
  21. KOWALEWSKI K., EMERY M. A. Effect of a lathyrus factor and of an anabolic steroid on healing of fractures in rats, studied by 35S uptake method. Acta Endocrinol (Copenh) 1960 Jun;34:317–322. doi: 10.1530/acta.0.xxxiv0317. [DOI] [PubMed] [Google Scholar]
  22. LEVENE C. I., GROSS J. Alterations in state of molecular aggregation of collagen induced in chick embryos by beta-aminopropionitrile (lathyrus factor). J Exp Med. 1959 Nov 1;110:771–790. doi: 10.1084/jem.110.5.771. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Lutwak-Mann C. Enzyme systems in articular cartilage. Biochem J. 1940 Apr;34(4):517–527. doi: 10.1042/bj0340517. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. MAJNO G., BUNKER W. E. Preparation of tissue slices for metabolic studies: a hand-microtome especially suitable for brain. J Neurochem. 1957;2(1):11–14. doi: 10.1111/j.1471-4159.1957.tb12347.x. [DOI] [PubMed] [Google Scholar]
  25. MIELKE J. E., LALICH J. J., ANGEVINE D. M. Influence of beta-aminopropionitrile upon development of connective tissue in croton oil pouches. Proc Soc Exp Biol Med. 1957 Apr;94(4):673–678. doi: 10.3181/00379727-94-23048. [DOI] [PubMed] [Google Scholar]
  26. MILLISER R. V., DASLER W. Osteolathyrism; histopathological lesions produced by semicarbazide and acetone semicarbazone. AMA Arch Pathol. 1959 Apr;67(4):427–431. [PubMed] [Google Scholar]
  27. McCALLUM H. M. Lathyrism in mice. Nature. 1958 Oct 25;182(4643):1169–1170. doi: 10.1038/1821169a0. [DOI] [PubMed] [Google Scholar]
  28. NEUMAN R. E., LOGAN M. A. The determination of hydroxyproline. J Biol Chem. 1950 May;184(1):299–306. [PubMed] [Google Scholar]
  29. PEDRINI V., PEDRINI-MILLE A. Decrease of enzymatic synthesis of hexosamine in epiphyseal plates of aminoacetonitrile-treated rabbits. Proc Soc Exp Biol Med. 1959 Jun;101(2):358–360. doi: 10.3181/00379727-101-24939. [DOI] [PubMed] [Google Scholar]
  30. PONSETI I. V. Lesions of the skeleton and of other mesodermal tissues in rats fed sweet-pea (Lathyrus odoratus) seeds. J Bone Joint Surg Am. 1954 Oct;36-A(5):1031–1058. [PubMed] [Google Scholar]
  31. PONSETI I. V., WAWZONEK S., SHEPARD R. S., EVANS T. C., STEARNS G. Further studies on lathyrism in the rat. Proc Soc Exp Biol Med. 1956 Jun;92(2):366–369. doi: 10.3181/00379727-92-22480. [DOI] [PubMed] [Google Scholar]
  32. PYORALA K., PUNSAR S., SEPPALA T., KARLSSON K. Mucopolysaccharides of the aorta and epiphyseal cartilage in lathyritic growing rats and rat fetuses. Acta Pathol Microbiol Scand. 1957;41(6):497–510. doi: 10.1111/j.1699-0463.1957.tb01716.x. [DOI] [PubMed] [Google Scholar]
  33. RAMAMURTI P., TAYLOR H. E. Histochemical studies of the evolution and regression of skeletal deformities due to betaaminopropionitril (BAPN). Lab Invest. 1958 Mar-Apr;7(2):115–125. [PubMed] [Google Scholar]
  34. Robinson C. V. Windowless, Flow Type, Proportional Counter for Counting C14. Science. 1950 Aug 18;112(2903):198–199. doi: 10.1126/science.112.2903.198. [DOI] [PubMed] [Google Scholar]
  35. SCHWARTZ C. J. The nature of the ground substance changes in experimental lathyrism and their effect on atherogenesis in cholesterol fed rabbits. Br J Exp Pathol. 1959 Feb;40(1):44–51. [PMC free article] [PubMed] [Google Scholar]
  36. VAN DEN HOOFF A., LEVENE C. I., GROSS J. Morphologic evidence for collagen changes in chick embryos treated with beta-aminopropionitrile. J Exp Med. 1959 Dec 1;110:1017–1022. doi: 10.1084/jem.110.6.1017. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. WIRTSCHAFTER Z. T. Acid mucopolysaccharides in the histopathogenesis of aortic aneurysms in the Lathyrus-fed rat. AMA Arch Pathol. 1957 Nov;64(5):577–583. [PubMed] [Google Scholar]

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