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E M Canalis

Publications and source records attributed to E M Canalis.

14 recordsLinked to original sources
PubMed1977

Hormonal control of bone collagen synthesis in vitro. Effects of insulin and glucagon.

The direct effects of porcine insulin and glucagon on bone collagen and non-collagen protein synthesis have been examined in cultures of calvaria obtained from 21-day fetal rats. Bones were incubated for 24 to 96 h and [3H]proline was added for the last 2 h of culture. Incorporation of the label into collagenase-digestible protein (CDP) and noncollagen protein (NCP) was determined using purified bacterial collagenase. Insulin increased the labeling of CDP by 60 to 115% at concentrations of 10(-9) to 10(-6) M. A smaller stimulatory effect was observed on NCP. The effect on CDP appeared after 12 to 24 h of culture, was maintained for 96 h in the continuous presence of the hormone, but was lost within 3 h of removal of insulin from the culture medium. Insulin appeared to have a direct effect on collagen synthesis and not on collagen breakdown. Insulin did not affect the incorporation of [3H]uridine or [3H]thymidine into the RNA and DNA fractions of bone at 24 h. Insulin opposed the inhibitory effects of parathyroid hormone and dibutyryl cyclic-3',5'-adenosine monophosphate and to a lesser extent, the inhibitory effect of isobutylmethylxanthine on the labeling of CDP. Glucagon did not affect the response to insulin and by itself had small and variable inhibitory effects on proline incorporation.

Animals↗
PubMed1976

Direct stimulation of bone resorption by thyroid hormones.

Although hypercalcemia, osteoporosis, and increased bone turnover are associated with thyrotoxicosis, no direct effects of thyroid hormones on bone metabolism have been reported previously in organ culture. We have now demonstrated that prolonged treatment with thyroxine (T4) or triiodothyronine (T3) can directly increase bone resorption in cultured fetal rat long bones as measured by the release of previously incorporated 45Ca. T4 and T3 at 1 muM to 10 nM increased 45Ca release by 10-60% of total bone 45Ca during 5 days of culture. The medium contained 4 mg/ml of bovine serum albumin to which 90% of T4 and T3 were bound, so that free concentrations were less than 0.1 muM. The response to T4 and T3 was inhibited by cortisol (1 muM) and calcitonin (100 mU/ml). Indomethacin did not inhibit T4 response suggesting that T4 stimulation of bone resorption was not mediated by increased prostaglandin synthesis by the cultured bone. Matrix resorption was demonstrated by a decrease in extracted dry weight and hydroxyproline concentration of treated bones and by histologic examination which also showed increased osteoclast activity. The effects of thyroid hormones were not only slower than those of other potent stimulators of osteoclastic bone resorption (parathyroid hormone, vitamin D metabolites, osteoclast activating factor, and prostaglandins), but the maximum response was not as great. We conclude that T4 and T3 can directly stimulate bone resorption in vitro at concentrations approaching those which occur in thyrotoxicosis. This effect may explain the disturbances of calcium metabolism seen in hyperthyroidism.

Animals↗
PubMed1976

Hormonal control of bone collagen synthesis in vitro: effects of parathyroid hormone and calcitonin.

The effects of parathyroid hormone (PTH) on bone collagen synthesis were assessed in organ cultures of fetal rat calvaria by measuring the incorporation of [3H]proline into collagenase-digestible (CDP) and non-collagen protein (NCP) using purified bacterial collagenase. 1) PTH decreased the incorporation of labeled proline into CDP at concentrations similar to those which stimulate bone resorption in vitro. 2) This effect was observed in bones treated for 6 h, but not for 3 h; it was maximal at 24 h and was maintained for 96 h. Bones treated with PTH for 48 h and transferred to control media for 48 h showed recovery of CDP labeling to control values. 3) the effect was specific for bone collagen. There was little alteration in the incorporation of proline into NCP, and incorporation into collagen was not inhibited. 4) The effect could be ascribed to decreased collagen synthesis and not to changes in amino acid uptake, precursor pool size, or degradation of newly synthesized CDP. In 3 hour experiments, PTH did increase the labeling of CDP and NCP, but only at tracer concentration of proline in the medium, compatible with an early stimulation of amino acid uptake. 5) Similar inhibition was observed with purified bovine (1-84) PTH and synthetic bovine PTH (1-34) as well as with crude homologous PTH obtained from rat parathyroid gland culture fluid. Human (hCT) and salmon (sCT) calcitonin did not inhibit the effect of PTH on the labeling of CDP nor did they stimulate CDP labeling directly at concentrations which inhibited bone resorption. Dibutyryl cyclic-3',5'-adenosine monophosphate (D3cAMP) inhibited labeling of CDP at concentrations of .03 to .3 mM, thus mimicking the action of PTH. However, in this system DBcAMP inhibited 45Ca release, thus mimicking CT. We conclude that the direct effect of PTH on bone collagen synthesis is a slow reversible inhibition, not opposed by CT. This effect may be mediated by cAMP formation in bone cells.

Animals↗