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. 1975 Nov;56(5):1181–1188. doi: 10.1172/JCI108195

Prostaglandin-stimulated bone resorption by rheumatoid synovia. A possible mechanism for bone destruction in rheumatoid arthritis.

D R Robinson, A H Tashjian Jr, L Levine
PMCID: PMC301982  PMID: 1184744

Abstract

Synovial tissue from patients with rheumatoid arthritis was maintained in organ culture for 3-14 days. Conditioned media from these synovial cultures contained bone resorption-stimulating activity, measured in vitro by using calcium release from mouse calvaria as the assay system. The synovial cultures also produce prostaglandin E2 (PGE2) as measured by serologic methods. The production of both the bone resorption-stimulating activity and PGE2 was inhibited by more than 90% by treatment of the synovial cultures with indomethacin (5 mug/ml). In contrast, treatment of the synovial cultures with colchicine (0.1 mug/ml) caused a marked and parallel increase in the concentration of both bone resorption-stimulating activity and PGE2 in the conditioned media. The bone resorption-stimulating activity was quantitatively extracted into diethyl ether. Within the limits of experimental error, all of the bone resorption-stimulating activity in medium was accounted for by its content of PGE2, itself a potent osteolytic factor. We conclude that the bone resorption-stimulating activity produced by rheumatoid synovia in culture is PGE2.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. COPP D. H. Simple and precise micromethod for EDTA titration of calcium. J Lab Clin Med. 1963 Jun;61:1029–1037. [PubMed] [Google Scholar]
  2. Ferraris V. A., DeRubertis F. R. Release of prostaglandin by mitogen- and antigen-stimulated leukocytes in culture. J Clin Invest. 1974 Aug;54(2):378–386. doi: 10.1172/JCI107773. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Fraser D. R., Kodicek E. Unique biosynthesis by kidney of a biological active vitamin D metabolite. Nature. 1970 Nov 21;228(5273):764–766. doi: 10.1038/228764a0. [DOI] [PubMed] [Google Scholar]
  4. Harris E. D., Jr, Cohen G. L., Krane S. M. Synovial collagenase: its presence in culture from joint disease of diverse etiology. Arthritis Rheum. 1969 Apr;12(2):92–102. doi: 10.1002/art.1780120206. [DOI] [PubMed] [Google Scholar]
  5. Horton J. E., Raisz L. G., Simmons H. A., Oppenheim J. J., Mergenhagen S. E. Bone resorbing activity in supernatant fluid from cultured human peripheral blood leukocytes. Science. 1972 Sep 1;177(4051):793–795. doi: 10.1126/science.177.4051.793. [DOI] [PubMed] [Google Scholar]
  6. Klein D. C., Raisz L. G. Prostaglandins: stimulation of bone resorption in tissue culture. Endocrinology. 1970 Jun;86(6):1436–1440. doi: 10.1210/endo-86-6-1436. [DOI] [PubMed] [Google Scholar]
  7. Levine L. Antibodies to pharmacologically active molecules: specificities and some applications of antiprostaglandins. Pharmacol Rev. 1973 Jun;25(2):293–307. [PubMed] [Google Scholar]
  8. Levine L., Gjtierrez Cernosek R. M., Van Vunakis H. Specificities of prostaglandins B 1 , F 1 , and F 2 antigen-antibody reactions. J Biol Chem. 1971 Nov 25;246(22):6782–6785. [PubMed] [Google Scholar]
  9. Mundy G. R., Luben R. A., Raisz L. G., Oppenheim J. J., Buell D. N. Bone-resorbing activity in supernatants from lymphoid cell lines. N Engl J Med. 1974 Apr 18;290(16):867–871. doi: 10.1056/NEJM197404182901601. [DOI] [PubMed] [Google Scholar]
  10. Omdahl J. L., DeLuca H. F. Regulation of vitamin D metabolism and function. Physiol Rev. 1973 Apr;53(2):327–372. doi: 10.1152/physrev.1973.53.2.327. [DOI] [PubMed] [Google Scholar]
  11. ROPES M. W., BENNETT G. A., COBB S., JACOX R., JESSAR R. A. 1958 Revision of diagnostic criteria for rheumatoid arthritis. Bull Rheum Dis. 1958 Dec;9(4):175–176. [PubMed] [Google Scholar]
  12. Robinson D. R., McGuire M. B., Levine L. Prostaglandins in the rheumatic diseases. Ann N Y Acad Sci. 1975 Jun 13;256:318–329. doi: 10.1111/j.1749-6632.1975.tb36058.x. [DOI] [PubMed] [Google Scholar]
  13. Tashjian A. H., Jr, Voelkel E. F., Goldhaber P., Levine L. Prostaglandins, calcium metabolism and cancer. Fed Proc. 1974 Jan;33(1):81–86. [PubMed] [Google Scholar]
  14. Tashjian A. H., Jr, Voelkel E. F., Levine L., Goldhaber P. Evidence that the bone resorption-stimulating factor produced by mouse fibrosarcoma cells is prostaglandin E 2 . A new model for the hypercalcemia of cancer. J Exp Med. 1972 Dec 1;136(6):1329–1343. doi: 10.1084/jem.136.6.1329. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Voelkel E. F., Tashjian A. H., Jr, Franklin R., Wasserman E., Levine L. Hypercalcemia and tumor-prostaglandins: the VX2 carcinoma model in the rabbit. Metabolism. 1975 Aug;24(8):973–986. doi: 10.1016/0026-0495(75)90089-x. [DOI] [PubMed] [Google Scholar]
  16. Weissmann G. Lysosomal mechanisms of tissue injury in arthritis. N Engl J Med. 1972 Jan 20;286(3):141–147. doi: 10.1056/NEJM197201202860307. [DOI] [PubMed] [Google Scholar]
  17. Ziff M. Relation of cellular infiltration of rheumatoid synovial membrane to its immune response. Arthritis Rheum. 1974 May-Jun;17(3):313–319. doi: 10.1002/art.1780170317. [DOI] [PubMed] [Google Scholar]

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