Dosing-time dependent effect of dexamethasone on bone density in rats

Takahashi, Masaki; Ushijima, Kazuo; Hayashi, Yohei; Maekawa, Toshiro; Ando, Hitoshi; Tsuruoka, Shuichi; Fujimura, Akio

doi:10.1016/j.lfs.2009.10.020

Cited by 9 publications

(10 citation statements)

References 39 publications

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“…Previous study found that Ob.S/BS and Oc.S/BS were decreased after GC treatment, with a reduction or maintaining of the trabecular bone volume [16]. But a reduction of cortical bone volume was always observed [16]. Previous data also demonstrated that bone loss in femoral cortical bone with no bone loss in the trabecular bone after GC treatment in adult mice [17].…”

Section: Discussionmentioning

confidence: 88%

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Glucocorticoid-Induced Osteoporosis in Growing Rats

et al. 2014

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This study evaluated whether growing rats were appropriate animal models of glucocorticoid-induced osteoporosis. The 3-month-old male rats were treated with either vehicle or prednisone acetate at 1.5, 3.0, and 6.0 mg/kg/day by oral gavage, respectively. All rats were injected with tetracycline and calcein before sacrificed for the purpose of double in vivo labeling. Biochemistry, histomorphometry, mechanical test, densitometry, micro-CT, histology, and component analysis were performed. We found that prednisone treatments dose dependently decreased body weight, serum biomarkers, biomechanical markers, bone formation, and bone resorption parameters in both tibial and femoral trabecular bone without trabecular bone loss. We also found that significant bone loss happened in femoral cortical bone in the glucocorticoid-treated rats. The results suggested that prednisone not only inhibited bone formation, but also inhibited bone resorption which resulted in poor bone strength but with no cancellous bone loss in growing rats. These data also suggested that the effects of glucocorticoid on bone metabolism were different between cortical bone and trabecular bone, and different between tibia and femur. Growing rats may be a glucocorticoid-induced osteoporosis animal model when evaluated the effects of drugs upon juvenile patients exposed to GC for a long time.

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Section: Discussionmentioning

confidence: 88%

Section: Discussionmentioning

confidence: 93%

Glucocorticoid-Induced Osteoporosis in Growing Rats

et al. 2014

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“…Some investigators found that bone marrow adipocytes could suppress osteoblast differentiation through secreting factors like PPARg, adiponectin or fatty acids (Gillet et al, 2017). Besides analyzing the bone tissue directly, biomarkers of bone turnover in serum or urine are frequently used to investigate the metabolic status of bone in both bench and clinical (Takahashi et al, 2010;Wheater et al, 2013). The statistical differences between DEX group and rLZ-8 groups in multiple biomarkers in serum and urine, suggested that rLZ-8 could affect multiple biomarkers in various processes.…”

Section: Discussionmentioning

confidence: 99%

Ganoderma lucidum Immune Modulator Protein rLZ-8 Could Prevent and Reverse Bone Loss in Glucocorticoids-Induced Osteoporosis Rat Model

et al. 2020

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Immune modulation has been recognized as an effective anti-osteoporosis strategy since the pivotal role of the RANK/RANKL/OPG signaling in bone metabolism and remodeling was discovered. To investigate the potential preventive and/or therapeutic effects of immune modulator protein Ling Zhi-8 (LZ-8) on osteoporosis, the osteoporosis animal model was established in Wistar rats by intramuscular injection of dexamethasone (DEX), namely glucocorticoids-induced osteoporosis (GIOP) rat model. To investigate the potential preventive effect of rLZ-8 on GIOP, we co-treated the rats with DEX and rLZ-8 intraperitoneally during the GIOP modeling stage and analyze the bone mass measured by bone mineral content (BMC) and bone mineral density (BMD), as well as levels of phosphorus (Pi), calcium (Ca 2+) and hydroxyproline (HOP) in femur of GIOP rats. Consistently, all results suggested that rLZ-8 could prevent bone loss in the femurs of GIOP rats. Through analyzing the trabeculae morphology and the trabeculae amount by H&E staining, we found rLZ-8 could also improve the structural deterioration in femurs of GIOP rats. In order to further verify the results and its mechanism obtained from bone analysis, multiple biomarkers, including minerals metabolism (Pi and Ca 2+), bone formation markers (osteocalcin, ALP and IGF-1), bone resorption markers (TRACP5b, CTX-1 and HOP), cytokines (IL-1b, IL-6 and TNF-a), oxidative stress indicators (GSH-px, SOD and MDA) and hormone molecules (testosterone, estradiol, calcitonin and parathyroid hormone) have been detected in serum or urine of rats. Results of these biomarkers in serum or urine confirmed rLZ-8's protective effect in GIOP. Through analyzing the relative expression level of OPG and RANKL in femurs via western blot, we foundrLZ-8 could increase OPG/RANKL ratio which could impede osteoclastogenesis process. To test the potential therapeutic effect of rLZ-8 on successfully generated GIOP rats, we administrated rLZ-8 to rats for three weeks starting from the ending day of 7 weeks treatment of DEX. We found rLZ-8 could also reverse the bone loss in GIOP rats. Through the BWs and organ coefficient analysis, we found rLZ-8 has little toxicity to the

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“…Glucocorticoid-induced osteoporosis is the third most common type of osteoporosis, preceded by postmenopausal and senile osteoporosis [14]. DEX is a commonly used glucocorticoid and studies have shown that DEX inhibited osteogenic differentiation and bone formation [15,16]. In this study, we showed that DEX can decrease the viability and ALP activity of MC3T3-E1 and miR-365 can significantly reverse this suppressive effect of DEX on MC3T3-E1.…”

Section: Discussionmentioning

confidence: 60%

miR-365 Ameliorates Dexamethasone-Induced Suppression of Osteogenesis in MC3T3-E1 Cells by Targeting HDAC4

Gao

et al. 2017

IJMS

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Glucocorticoid administration is the leading cause of secondary osteoporosis. In this study, we tested the hypotheses that histone deacetylase 4 (HDAC4) is associated with glucocorticoid-induced bone loss and that HDAC4 dependent bone loss can be ameliorated by miRNA-365. Our previous studies showed that miR-365 mediates mechanical stimulation of chondrocyte proliferation and differentiation by targeting HDAC4. However, it is not clear whether miR-365 has an effect on glucocorticoid-induced osteoporosis. We have shown that, in MC3T3-E1 osteoblasts, dexamethasone (DEX) treatment decreased the expression of miR-365, which is accompanied by the decrease of cell viability in a dose-dependent manner. Transfection of miR-365 ameliorated DEX-induced inhibition of MC3T3-E1 cell viability and alkaline phosphatase activity, and attenuated the suppressive effect of DEX on runt-related transcription factor 2 (Runx2), osteopontin (OPN), and collagen 1a1 (Col1a1) osteogenic gene expression. In addition, miR-365 decreased the expression of HDAC4 mRNA and protein by direct targeting the 3′-untranslated regions (3′-UTR) of HDAC4 mRNA in osteoblasts. MiR-365 increased Runx2 expression and such stimulatory effect could be reversed by HDAC4 over-expression in osteoblasts. Collectively, our findings indicate that miR-365 ameliorates DEX-induced suppression of cell viability and osteogenesis by regulating the expression of HDAC4 in osteoblasts, suggesting miR-365 might be a novel therapeutic agent for treatment of glucocorticoid-induced osteoporosis.

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Dosing-time dependent effect of dexamethasone on bone density in rats

Abstract: This study shows that the decrease in bone density induced by Dex was changed by its dosing-time.

Cited by 9 publications

References 39 publications

Glucocorticoid-Induced Osteoporosis in Growing Rats

Glucocorticoid-Induced Osteoporosis in Growing Rats

Ganoderma lucidum Immune Modulator Protein rLZ-8 Could Prevent and Reverse Bone Loss in Glucocorticoids-Induced Osteoporosis Rat Model

miR-365 Ameliorates Dexamethasone-Induced Suppression of Osteogenesis in MC3T3-E1 Cells by Targeting HDAC4

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