A micropuncture study of growth cartilage in phosphonate (EHDP) induced rickets
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Evidence in the cartilage for influence of EHDP on mineralization processes was found by the biochemical examination of nanoliter samples (Cfl) aspirated in vivo from the upper tibial growth plate of rats subjected to a regimen of EHDP. The induced rachitic syndrome was distinctively different from that resulting from lack of vitamin D and low-phosphate rachitogenic diet (−VDP). Significant findings were the following: (a) the Cfl phosphate concentration was about half that in the serum; (b) the proteoglycan concentration was depleted to about 20% of the value in both −VDP rachitic and normal control rats. These macromolecules, however, exhibited an abnormally high average sedimentation coefficient as if all the molecules were organized as large aggregates; (c) the lysozyme activity, easily detectable in the normal controls (equivalent to that of 50µg/ml of egg white lysozyme), was not detectable. Also, unlike the −VDP rickets, the calcium and phosphate concentration product was, although smaller than in the controls, high enough to sustain mineral growth in vitro.
The corresponding recovery processes from both types of rickets, the −VDP and the EHDP, were studied in Cfl samples from rats 3 days after the drug withdrawal in the latter group, or after restoring the vitamin D and the phosphate in the −VDP group. It is interesting that in spite of the initial differences, parameters relevant to calcification displayed similar values in rats undergoing recuperation from both types of rickets. Consistent with the hypothesis that proteoglycan aggregates regulate cartilage calcification, the average sedimentation coefficient decreased from 127S to about 50S in rats healing from EHDP rickets.
Key wordsMineralization Growth plates Phosphonates
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- 1.Russell, R.G.G., Smith, R.: Diphosphonates, J. Bone Joint Surg.55:66–86, 1973Google Scholar
- 2.Fleisch, H., Russell, R.G.G., Bisaz, S., Bonjour, J.P.: The effects of pyrophosphate and diphosphonates on calcium metabolism. Hard tissue growth, repair and remineralization, Ciba Found. Symp.11:331–358, 1973Google Scholar
- 3.Jung, A., Bisaz, S., Fleisch, H.: The binding of pyrophosphate and two diphosphonates by hydroxyapatite crystals, Calcif. Tissue Res.9:140–151, 1973Google Scholar
- 5.Schenk, R., Merz, W.A., Mühlbauer, R., Russell, R.G.G., Fleisch, H.: Effect of ethane-1-hydroxy-1,1-diphosphonate (EHDP) and dichloromethylene diphosphonate (Cl2MDP) on the calcification and resorption of cartilage and bone in the tibial epiphysis and metaphysis of rats, Calcif. Tissue Res.11:196–214, 1973PubMedGoogle Scholar
- 7.Larsson, A., Larsson, S.E.: Light microscopic and ultrastructural observations on the short-term effects of ethylene-1-hydroxy-1,1-diphosphonate (EHDP) on rat tibia epiphysis, Acta Pathol. Microbiol. Scand.84:17–27, 1976Google Scholar
- 13.Pita, J.C., Muller, F.J., Howell, D.S.: Disaggregation of proteoglycan aggregate during endochondral calcification: physiological role of cartilage lysozyme. In P.M.C. Burleigh, A.R. Poole (eds): Dynamics of Connective Tissue Macromolecules, pp. 247–258. North-Holland Publishing Co., Amsterdam, 1974Google Scholar
- 17.Ramsay, J.A., Brown, R.H.J., Croghan, P.C.: Electrometric titration of chloride in small volumes, J. Exp. Biol.32:822–829, 1955Google Scholar
- 28.Kuettner, K.E., Sorgente, N., Croxen, R., Howell, D.S., Pita, J.C.: Lysozyme in preosseous cartilage. VII. Evidence for a physiological role of lysozyme in normal endochondral calcification, Biochim. Biophys. Acta372:335–344, 1974Google Scholar
- 29.Hascall, V.C., Heinegard, D.: The structure of cartilage proteoglycans. In H.C. Slavkin, R.C. Greulich (eds.): Extracellular Matrix Influences on Gene Expression, pp. 423–433. Academic Press, New York, 1975Google Scholar
- 36.Boskey, A.L., Goldberg, M.R., Posner, A.S.: The effect of diphosphonates on the formation of hydroxyapatite induced by calcium-phospholipid-phosphate complexes, Calcif. Tissue Int.Google Scholar