Dexamethasone suppresses in vivo levels of bone collagen synthesis in neonatal mice

doi:10.1016/S8756-3282(96)00314-6

Bone

Volume 20, Issue 1, January 1997, Pages 41-46

https://doi.org/10.1016/S8756-3282(96)00314-6 Get rights and content

Abstract

The objective of this study was to determine the acute effects of glucocorticoids on in vivo levels of bone collagen synthesis in neonatal mice. Mice were injected with vehicle or dexamethasone at the start of the experiment. At 22 h, mice were given a 10 μCi injection of [³H]proline. At 24 h, the mice were sacrificed and the incorporation of [³H]proline into collagenase-digestible CDP labeling) and noncollagen (NCP labeling) protein in calvariae were determined by digestion with bacterial collagenase. Calvarial RNA was analyzed for COL 1A1 and osteocalcin mRNA levels by Northern blotting. After 24 h, vehicle-treated mice showed a 9.8 ± 1.0% weight gain while dexamethasone-treated mice (1 mg/kg) had a 7.4 ± 0.8% weight loss. Dexamethasone (1 mg/kg) decreased CDP and NCP labeling in calvariae by 51 ± 4% and 17 ± 4%, respectively (13 experiments). The inhibitory effect on protein labeling was selective for collagen since dexamethasone decreased the percent collagen synthesis from 25.4 ± 1.6% to 16.6 ± 1.0% (13 experiments). Dexamethasone at 3 mg/kg also decreased CDP labeling and the percent collagen synthesis in calvariae. There was a 30% reduction in COL1A1 mRNA levels and a 67% decrease in osteocalcin mRNA levels. To determine the reversibility of the inhibition of collagen synthesis, mice were given a single injection of dexamethasone (1 mg/kg) and then injected with [³H]proline 2 h prior to sacrifice at 24, 48, or 72 h. The reduction in CDP labeling observed at 24 h was fully reversed by 48–72 h. Moreover, by 72 h, the rate of weight gain by dexamethasone-treated mice was similar to vehicle-treated controls. These data show that administration of dexamethasone to neonatal mice leads to a selective decrease in bone collagen synthesis within 24 h that is accompanied by down-regulation of osteocalcin and COL1A1 mRNA levels. This model will be useful in determining mechanisms by which high dose glucocorticoids inhibit bone formation in vivo.

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The results corroborate those of previous studies that showed the interference of GCs with the formation of collagen and osteoid matrix (Advani et al., 1997; Gronowicz, DeRome, & McCarthy, 1991; Li et al., 2012; Lukert, Mador, Raisz, & Kream, 1991). Advani et al. (1997) showed decreased collagen synthesis in calvarial defects in rats, 24 h after administering a single dose of 1 mg/kg of dexamethasone. The authors observed reductions in levels of messenger ribonucleic acid (mRNA) of collagen 1A1 (Col1A1) and osteocalcin.
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Original articleDexamethasone suppresses in vivo levels of bone collagen synthesis in neonatal mice

Abstract

Dev Biol

Exp Cell Res

J Biol Chem

Biochem Biophys Res Commun

Blood

J Biol Chem

Dev Biol

Am J Med

Steroid-induced fractures and bone loss in patients with asthma

New Engl J Med

Interactions between growth hormone and dexamethasone in skeletal growth and bone structure of the young mouse

Calcif Tissue Int

Physiologic concentrations of glucocorticoids stimulate formation of bone nodules from isolated rat calvaria cells in vitro

Endocrinology

Upstream regulatory elements necessary for expression of the rat COL1A1 promoter in transgenic mice

J Bone Miner Res

Histomorphometric profile, pathophysiology, and reversibility of corticosteroid-induced osteoporosis

Metab Bone Dis Rel Res

Effect of glucocorticoids on type I collagen synthesis, alkaline phosphatase activity, and deoxyribonucleic acid content in cultured rat calvariae

Endocrinology

Effect of cortisol on periosteal and nonperiosteal collagen and DNA synthesis in cultured rat calvariae

Calcif Tissue Int

Glucocorticoid receptors and actions in subpopulations of cultured rat bone cells. Mechanism of dexamethasone protentiation of parathyroid hormone-stimulated cyclic AMP production

J Clin Invest

Differentiation of human bone marrow osteogenic stromal cells in vitro: Induction of the osteoblast phenotype by dexamethasone

Endocrinology

Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction

Anal Biochem

Cortisol decreases bone formation by inhibiting periosteal cell proliferation

Endocrinology

Glucocorticoids decrease the synthesis of type I procollagen mRNA

Biochemistry

The basophil adenomas of the pituitary and their clinical manifestations

Bull Johns Hopkins Hosp

Cortisol downregulates osteoblast alphal (1) procollagen mRNA by transcriptional and posttranscriptional mechanisms

J Cell Biochem

Bone histomorphology in glucocorticoid-induced osteoporosis

J Bone Miner Res

Mean wall thickness and formation periods of trabecular bone packets in corticosteroid-induced osteoporosis

Calcif Tissue Int

Effects of glucocorticoids on fetal rat bone collagen synthesis in vitro

Endocrinology

The effect of glucocorticoids on osteoblast function: The effect of corticosterone on osteoblast expression of beta-1 integrins

J Bone Joint Surgery

Original article
Dexamethasone suppresses in vivo levels of bone collagen synthesis in neonatal mice