Summary
Osteoclast activating factor (OAF) is a lymphokine which may participate in the pathologic destruction of bone observed in a number of disorders. In the current studies, we investigated the action of OAF on cAMP accumulation by bones and isolated bone cells in culture. OAF was shown to stimulate accumulation of cAMP in mouse cranial bones at doses between 1 and 1000 ng/ml. Stimulation of bone resorption was observed in bones treated with the same doses of OAF. In order to investigate the cell types responsible for cAMP responses to OAF, we isolated bone cells and grew them in monolayer culture. The cells were isolated by a variety of techniques which separate bone cells into two types of parathyroid hormone (PTH)-responsive populations: (a) cells derived from the periosteal regions of the bone, which also respond to calcitonin with increases in cAMP; and (b) cells derived from the matrix, which do not respond to calcitonin. OAF caused elevation of cAMP levels in both the periosteum-derived cells and the matrix-derived cells. The magnitudes and time courses of OAF effects in these populations resembled the effects previously reported for PTH in the same populations. OAF stimulated adenyl cyclase in both types of cell populations, but did not produce significant changes in cAMP phosphodiesterase activity. OAF differed from PTH in that its effects on cAMP accumulation decreased sharply at supramaximal doses in both bone and isolated cells, especially in the matrix-derived populations. Bone resorption did not decrease as markedly as did cAMP accumulation at high doses of OAF, suggesting that cAMP accumulation and resorption could be dissociated under some conditions. These results indicate that OAF has effects on cAMP production in the same cell populations as PTH, and suggest that OAF could modify not only resorption but also formation of bone in vivo. OAF may exert its effects on bone by means of cAMP-dependent mechanisms, but more data will be necessary to establish this unequivocally. The observed differences between OAF and PTH may be of relevance in the mechanism and treatment of pathologic bone destruction in vivo.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
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, Science72:793–795, 1972
Luben, R.A., Mundy, G.R., Trummel, C.L., Raisz, L.G.: Partial purification of osteoclast activating factor from phytohemagglutinin stimulated human leukocytes, J. Clin. Invest.53:1473–1480, 1974
Luben, R.A.: Purification of a lymphokine: Osteoclast activating factor from human tonsil lymphocytes, Biochem. Biophys. Res. Commun.84:15–22, 1978
Mundy, G.R., Raisz, L.G., Cooper, R.A., Schechter, G.P., Salmon, S.E.: Evidence for the secretion of an osteoclast stimulating factor in myeloma, N. Engl. J. Med.291:1041–1046, 1974
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.290:867–871, 1974
Manson, J.D.: Bone morphology and bone loss in periodontal disease, J. Clin. Periodont.3:14–22, 1976
Adatia, A.K.: Dental tissues and Burkitt's tumor, Oral Surg.25:221–234, 1968
Luben, R.A.: Development of an assay for osteoclast activating factor in biological fluids, Proceedings, Mechanisms of Bone Loss, Calcified Tissue Abstracts (Special Supplement), p. 438, 1978
Raisz, L.G., Luben, R.A., Mundy, G.F., Dietrich, J.W., Horton, J.E., Trummel, C.L.: Effect of osteoclast activating factor from human leukocytes on bone metabolism, J. Clin. Invest.56:408–413, 1975
Dietrich, J.W., Canalis, E.M., Maina, D.M., Raisz, L.G.: Hormonal control of bone collagen synthesisin vitro: effects of parathyroid hormone and calcitonin, Endocrinology98:943–949, 1976
Chase, L.R., Aurbach, G.D.: The effect of parathyroid hormone on the concentration of adenosine 3′,5′-monophosphate in skeletal tissuein vitro, J. Biol. Chem.245:1520–1526, 1970
Luben, R.A., Wong, G.L., Cohn, D.V.: Biochemical characterization with parathormone and calcitonin of isolated bone cells: provisional identification of osteoclasts and osteoblasts, Endocrinology99:526–534, 1976
Wong, G.L., Luben, R.A., Cohn, D.V.: 1,25-Dihydroxycholecalciferol and parathormone: effects on isolated osteoclast-like and osteoblast-like cells, Science197:663–665, 1977
Peck, W.A., Dowling, I.: Failure of 1,25 dihydroxycholecalciferol to modify cyclic AMP levels in parathyroid hormone-treated and untreated bone cells, Endocrine Res. Commun.3:157–166, 1976
Peck, W.A., Birge, S.J., Fedak, S.A.: Bone cells: Biochemical and biological studies after enzymatic isolation, Science146:1476–1477, 1964
Chen, T.L., Feldman, D.: Glucocorticoid actions on different cultured bone cell populations and modulation of the response to parathyroid hormone, Endocrinology102(Suppl):142, 1978
Wong, G., Cohn, D.V.: Separation of parathyroid hormone and calcitonin-sensitive cells from non-responsive bone cells, Nature252:713–715, 1974
Smith, D.M., Johnston, C.C.: Cyclic 3′,5′-adenosine monophosphate levels in separated bone cells, Endocrinology96:1261–1269, 1975
Luben, R.A., Cohn, D.V.: Effects of parathormone and calcitonin on citrate and hyaluronate metabolism in cultured bone, Endocrinology98:413–419, 1976
Harper, J.F., Brooker, G.: Femtomole sensitive radioimmunoassay for cyclic AMP and cyclic GMP after 2′0 acetylation by acetic anhydride in aqueous solution, J. Cyclic Nucleotide Res.1:207–218, 1975
Dziak, R., Stern, P.H.: Calcium transport in isolated bone cells III. Effects of parathyroid hormone and cyclic 3′—5′ AMP, Endocrinology97:1281–1287, 1975
Steiner, A.L., Parker, C.W., Kipnis, D.M.: Radioimmunoassay for cyclic nucleotides. I. Preparation of antibodies and iodinated cyclic nucleotides, J. Biol. Chem.247:1106–1113, 1972
Rodbard, D., Rayford, P.L., Cooper, J.A., Ross, G.T.: Statistical quality control of radioimmunoassays, J. Clin. Endocrinol. Metab.28:1412–1418, 1968
Gilman, A.G.: A protein binding assay for adenosine 3′,5′-cyclic monophosphate, Proc. Natl. Acad. Sci. (U.S.A.)67:305–312, 1970
Rapoport, B., Adams, R.J.: Induction of retractoriness to thyrotropin stimulation in cultured thyroid cells. Dependence on new protein synthesis, J. Biol. Chem.251:6653–6661, 1976
Lenox, R.H., Meyerhoff, J.L., Gandhi, O.P., Wray, H.L.: Regional levels of cyclic AMP in rat brain: pitfalls of microwave inactivation, J. Cyclic Nucleotide Res.3:367–379, 1977
Dunnett, C.W.: New tables for multiple comparisons with a control, Biometrics20:482–491, 1964
Aaron, J.E.: Osteocyte types in the developing mouse calvarium, Calcif. Tissue Res.12:259–279, 1973
Luben, R.A., Mohler, M.A., Rosen, D.M.: Evaluation of a new method for studying resorption by isolated bone cells. In A.W. Norman et al. (eds.): Vitamin D: Biochemical, Chemical and Clinical Aspects Related to Calcium Metabolism, pp. 395–397. Walter de Gruyter, New York, 1977
Marcus, R., Orner, F.B.: Cyclic AMP production in rat calvariain vitro: interaction of prostaglandins with parathyroid hormone, Endocrinology101:1570–1578, 1977
Rosenblatt, M., Callahan, E.N., Mahaffey, J.E., Pont, A., Potts, J.T.: Parathyroid hormone inhibitors. Design, synthesis and biologic evaluation of hormone analogues, J. Biol. Chem.252:5847–5851, 1977
Vaes, G.: Parathyroid hormone-like action of N6-2′-0-dibutyryladenosine 3′5′ cyclic monophosphate on bone explants in tissue culture, Nature219:939–940, 1968
Klein, D.C., Raisz, L.G.: Role of adenosine-3′5′-monophosphate in the hormonal regulation of bone resorption: studies with cultured fetal bone, Endocrinology89:818–826, 1971
Dziak, R., Stern, P.: Responses of fetal rat bone cells and bone organ cultures to the ionophore, A23187, Calcif. Tissue Res.22:137–147, 1976
Hermann-Erlee, M.P.M., Gaillard, P.J., Hekkelman, J.W.: Regulation of the response of embryonic bone to PTH and PTH fragments. A morphological and biochemical study. In D.H. Copp, R.V. Talmage (eds.): Endocrinology of Calcium Metabolism, pp. 253–261. Excerpta Medica, Amsterdam, 1978
Wong, G.L., Kent, G.N., Ku, K.K., Cohn, D.V.: The interaction of parathormone and calcium on the hormone-regulated synthesis of hyaluronic acid and citrate decarboxylation in isolated bone cells, Endocrinology103:2274–2282, 1978
Koopman, W.J., Gillis, M.H., David, J.R.: Prevention of MIF activity by agents known to increase cellular cyclic AMP, J. Immunol.110:1609–1614, 1973
Okamoto, M., Mayer, M.M.: Studies on the mechanism of action of guinea pig lymphotoxin. II. Increase of calcium uptake in LT-damaged target cells, J. Immunol.120:279–285, 1978
Jegasothy, B.V., Packner, A.R., Waksman, B.H.: Cytokine inhibition of DNA synthesis: effect on cyclic adenosine monophosphate in lymphocytes, Science193:1260–1262, 1976
Oppenheim, J.J., Shneyour, A., Kook, A.I.: Enhancement of DNA synthesis and cAMP content of mouse thymocytes by mediators derived from adherent cells, J. Immunol.116:1466–1472, 1976
Waksman, B.H., Wagshal, A.B.: Lymphocytic functions acted on by immunoregulatory cytokines. Significance of the cell cycle, Cell. Immunol.36:180–196, 1978
Marcus, W.: Cyclic nucleotide phosphodiesterase from bone: characterization of the enzyme and studies of inhibition by thyroid hormones, Endocrinology96:400–408, 1975
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Luben, R.A., Chen, M.CY., Rosen, D.M. et al. Effects of osteoclast activating factor from human lymphocytes on cyclic AMP concentrations in isolated mouse bone and bone cells. Calcif Tissue Int 28, 23–32 (1979). https://doi.org/10.1007/BF02441214
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02441214