Stimulation of Bone Resorption by Parathyroid Hormone in Tissue Culture

Nature ◽  
1963 ◽  
Vol 197 (4871) ◽  
pp. 1015-1016 ◽  
Author(s):  
LAWRENCE G. RAISZ
Keyword(s):  
Tissue Culture ◽  
Parathyroid Hormone ◽  
Bone Resorption ◽  
Stimulation Of

Interaction between amrinone and parathyroid hormone on bone in culture

1982 ◽  
Vol 243 (6) ◽  
pp. E499-E504
Author(s):  
N. S. Krieger ◽  
P. H. Stern
Keyword(s):  
Parathyroid Hormone ◽  
Bone Resorption ◽  
Direct Interaction ◽  
Inhibitory Effects ◽  
Dihydroxyvitamin D3 ◽  
Basal Bone ◽  
Cardiotonic Agent ◽  
Neonatal Mouse Calvaria ◽  
Dose Dependent ◽  
Stimulation Of

The cardiotonic agent amrinone has been postulated to directly affect Na-Ca exchange. Because stimulated bone resorption has been proposed to require Na-Ca exchange, we examined the effects of amrinone on bone. Amrinone inhibited release of Ca from neonatal mouse calvaria in organ culture stimulated by parathyroid hormone (PTH), 1,25-dihydroxyvitamin d3, or prostaglandin E2. Inhibition was dose dependent and maximal at 2 X 10(-4) M. The effect of amrinone differed from the inhibitory effects of calcitonin, ouabain, or nigericin in that 1) 6-h exposure to amrinone alone prevented the effect of subsequently added PTH; 2) amrinone was only partially effective if added after resorption was initiated by 24-h treatment with PTH; 3) coincubation with amrinone and PTH during the first 48 h of culture allowed for a response to PTH after amrinone was removed; no such protection by a stimulator occurred with ouabain or nigericin. Also submaximal concentrations of amrinone plus calcitonin, ouabain, or nigericin gave greater than additive inhibition of Ca release. Amrinone had no effect on basal bone cAMP or on the acute stimulation of cAMP by PTH. The results suggest that amrinone could have a more direct interaction with the pathway involved in stimulated bone resorption than the other inhibitors.

scholarly journals ON THE MECHANISMS OF BONE RESORPTION

1968 ◽  
Vol 39 (3) ◽  
pp. 676-697 ◽  
Author(s):  
Gilbert Vaes
Keyword(s):  
Tissue Culture ◽  
Alkaline Phosphatase ◽  
Protein Synthesis ◽  
Bone Resorption ◽  
Bone Mineral ◽  
Lysosomal Enzymes ◽  
Organic Matrix ◽  
Acid Hydrolases ◽  
New Synthesis ◽  
Stimulation Of

Bone resorption, characterized by the solubilization of both the mineral and the organic components of the osseous matrix, was obtained in tissue culture under the action of parathyroid hormone (PTH). It was accompanied by the excretion of six lysosomal acid hydrolases, which was in good correlation with the progress of the resorption evaluated by the release of phosphate, calcium 45 or hydroxyproline from the explants; there was no increased excretion of two nonlysosomal enzymes, alkaline phosphatase, and catalase. Balance studies and experiments with inhibitors of protein synthesis indicated that the intracellular stores of the acid hydrolases excreted were maintained by new synthesis. The release was not due to a direct disruption of the lysosomal membrane by PTH; it is presumed to result from an exocytosis of the whole lysosomal content and to involve mechanisms similar to those controlling the secretion of this content into digestive vacuoles. The resorbing explants acidified their culture fluids at a faster rate and released more lactate and citrate than the controls; this release was in good correlation, in the PTH-treated cultures, with the resorption of the bone mineral, but the amount of citrate released was considerably smaller than that of lactate. The acid released could account for the resorption of the mineral. It is proposed, as a working hypothesis, that the acid hydrolases of the lysosomes are active in the resorption of the organic matrix of bone and that acid, originating possibly from the stimulation of glycolysis, cares for the concomitant solubilization of bone mineral while also favoring the hydrolytic action of the lysosomal enzymes.

scholarly journals SIKs control osteocyte responses to parathyroid hormone

2016 ◽  
Vol 7 (1) ◽  
Author(s):  
Marc N. Wein ◽  
Yanke Liang ◽  
Olga Goransson ◽  
Thomas B. Sundberg ◽  
Jinhua Wang ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Bone Resorption ◽  
Bone Formation ◽  
Small Molecule ◽  
Nuclear Translocation ◽  
Rna Seq ◽  
Once Daily ◽  
Skeletal Effects ◽  
Stimulation Of

Abstract Parathyroid hormone (PTH) activates receptors on osteocytes to orchestrate bone formation and resorption. Here we show that PTH inhibition of SOST (sclerostin), a WNT antagonist, requires HDAC4 and HDAC5, whereas PTH stimulation of RANKL, a stimulator of bone resorption, requires CRTC2. Salt inducible kinases (SIKs) control subcellular localization of HDAC4/5 and CRTC2. PTH regulates both HDAC4/5 and CRTC2 localization via phosphorylation and inhibition of SIK2. Like PTH, new small molecule SIK inhibitors cause decreased phosphorylation and increased nuclear translocation of HDAC4/5 and CRTC2. SIK inhibition mimics many of the effects of PTH in osteocytes as assessed by RNA-seq in cultured osteocytes and following in vivo administration. Once daily treatment with the small molecule SIK inhibitor YKL-05-099 increases bone formation and bone mass. Therefore, a major arm of PTH signalling in osteocytes involves SIK inhibition, and small molecule SIK inhibitors may be applied therapeutically to mimic skeletal effects of PTH.

Parathyroid hormone sensitizes long bones to the stimulation of bone resorption by 1,25-dihydroxyvitamin D3

2009 ◽  
Vol 7 (3) ◽  
pp. 303-309 ◽  
Author(s):  
J. P. T. M. van Leeuwen ◽  
J. C. Birkenhäger ◽  
M. P. Bos ◽  
G. J. C. M. van der Bemd ◽  
M. P. M. Herrmann-Erlee ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Bone Resorption ◽  
Long Bones ◽  
Dihydroxyvitamin D3 ◽  
1,25 Dihydroxyvitamin D3 ◽  
Stimulation Of

Thyrocalcitonin Inhibition of Bone Resorption Induced by Parathyroid Hormone in Tissue Culture

Science ◽  
1966 ◽  
Vol 151 (3708) ◽  
pp. 330-331 ◽  
Author(s):  
M. A. Aliapoulios ◽  
P. Goldhaber ◽  
P. L. Munson
Keyword(s):  
Tissue Culture ◽  
Parathyroid Hormone ◽  
Bone Resorption
Sign in / Sign up

Export Citation Format

Share Document