Dynamic expression of Runx2, Osterix and AJ18 in the femoral head of steroid-induced osteonecrosis in rats

Ma, Xinlong; Liu, Zepeng; Ma, Jianxiong; Han, Chao; Zang, Jiacheng

doi:10.1111/j.1757-7861.2010.00100.x

Cited by 27 publications

(23 citation statements)

References 14 publications

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“…As detailedly described in the Methods part, we administered low dose of dexamethasone sodium phosphate every 24 hours for three times in total, which could successfully establish rat models of ONFH and lead to a lower mortality rate, compared with the traditional way of injecting a much higher dose on 7-day interval for three times in total323334. Our previous studies prove that interval injection with a higher dose is more applicable in establishing animal models with a larger body figure such as rabbits.…”

Section: Discussionmentioning

confidence: 99%

miR-27a attenuates adipogenesis and promotes osteogenesis in steroid-induced rat BMSCs by targeting PPARγ and GREM1

Zhang

et al. 2016

Sci Rep

100

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The imbalance between adipogenic and osteogenic differentiation in bone marrow mesenchymal stem cells (BMSCs) plays a significant role in the pathogenesis of steroid-induced osteonecrosis of the femoral head (ONFH). Several microRNAs (miRNAs) are involved in regulating adipogenesis and osteogenesis. In this study, we established a steroid-induced ONFH rat model to identify the potential relevant miRNAs. We identified 9 up-regulated and 28 down-regulated miRNAs in the ONFH rat model. Of these, miR-27a was down-regulated and negatively correlated with peroxisome proliferator-activated receptor gamma (PPARγ) and gremlin 1 (GREM1) expression. Further studies confirmed that PPARγ and GREM1 were direct targets of miRNA-27a. Additionally, adipogenic differentiation was enhanced by miR-27a down-regulation, whereas miRNA-27a up-regulation attenuated adipogenesis and promoted osteogenesis in steroid-induced rat BMSCs. Moreover, miRNA-27a up-regulation had a stronger effect on adipogenic and osteogenic differentiation in steroid-induced rat BMSCs than si-PPARγ and si-GREM1. In conclusion, we identified 37 differentially expressed miRNAs in the steroid-induced ONFH model, of which miR-27a was down-regulated. Our results showed that miR-27a up-regulation could inhibit adipogenesis and promote osteogenesis by directly targeting PPARγ and GREM1. Thus, miR-27a is likely a key regulator of adipogenesis in steroid-induced BMSCs and a potential therapeutic target for ONFH treatment.

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Section: Discussionmentioning

confidence: 99%

miR-27a attenuates adipogenesis and promotes osteogenesis in steroid-induced rat BMSCs by targeting PPARγ and GREM1

Zhang

et al. 2016

Sci Rep

100

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“…Under physiological conditions, NO is released by the vascular endothelium and serves an important protective role for endothelial function (27). ET contents in the circulation are low under physiological conditions, and its effects on the endothelium are negligible (27).…”

Section: Discussionmentioning

confidence: 99%

Cardioprotective effects of anisodamine against myocardial ischemia/reperfusion injury through the inhibition of oxidative stress, inflammation and apoptosis

Yao

Lin

et al. 2017

Mol Med Report

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The aim of the present study was to investigate the cardioprotective effects of anisodamine against myocardial ischemia/reperfusion (I/R) injury and the molecular mechanisms involved. The present results demonstrated that anisodamine attenuated myocardial infarct sizes, decreased the levels of creatine kinase and lactate dehydrogenase, whereas it increased the left ventricular (LV) systolic pressure, the LV end‑diastolic pressure, and the LV pressure maximum rising and falling rates in a myocardial I/R rat model. In addition, anisodamine was revealed to suppress oxidative stress, inflammatory factor production and myocardial cell apoptosis, as demonstrated by the downregulation of caspase‑3 and apoptosis regulator BAX protein expression. The production of reactive oxygen species was decreased and the protein expression of inducible nitric oxide synthase (iNOS) was downregulated, whereas the expression of endothelial NOS was enhanced. In addition, the activity of nicotinamide‑adenine dinucleotide phosphate oxidase (Nox) was suppressed and the expression of Nox4 was downregulated in rats with myocardial I/R injury. In conclusion, the results of the present study suggested that anisodamine exerted a cardioprotective effect against myocardial I/R injury in rats, through the inhibition of oxidative stress, the suppression of inflammatory processes and the inhibition of myocardial cell apoptosis.

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“…Osteonecrosis was defined as previously described (27,28,31) and the incidence of SAON in rats was defined as the number of femoral heads with predominant empty lacunae divided by six femoral heads in each group. Number data were expressed as the mean AE SD with ANOVA (Fisher's least significant difference [LSD]) method to assess significant differences between groups.…”

Section: Discussionmentioning

confidence: 99%

TET3 Mediates Alterations in the Epigenetic Marker 5hmC and Akt pathway in Steroid-Associated Osteonecrosis

Zhao

et al. 2016

Journal of Bone and Mineral Research

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Steroid-associated osteonecrosis (SAON) is one of the common complications of clinical glucocorticoid (GC) administration, with osteocyte apoptosis appearing as the primary histopathological lesion. However, the precise mechanism underlying SAON remains unknown. Epigenetic modification may be a major cause of SAON. Recently, cumulative research revealed that Ten-Eleven Translocation (TET) proteins can catalyze the conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) and then alter the epigenetic state of DNA. Here, we report that TET3-5hmC was upregulated in the femoral head tissues of SAON patients and MLO-Y4 cells with dexamethasone (Dex) treatment. Knockdown of TET3 in MLO-Y4 cells decreased 5hmC enrichment and rescued Dex-induced apoptosis. Meanwhile, the local intramedullary injection of TET3 siRNA in Sprague-Dawley rats abrogated GC-induced osteocyte apoptosis, histopathological changes, abnormal MRI signals, and bone microstructure declines in the femoral head in vivo. Moreover, a hydroxymethylated DNA immunoprecipitation (hMeDIP)-chip analysis of Dex-treated osteocytes revealed 456 different 5hmC-enriched genes. The Akt pathway was found to mediate the functional effect of Dex-induced dynamic 5hmC change; this was further verified in clinical samples. The loss of TET3 in MLO-Y4 cells abrogated Dex-induced Akt signaling pathway inhibition. Therefore, our data for the first time identify the effect of TET3-5hmC on the Akt pathway and the necessity of this signaling cascade in SAON, identifying a new potential therapeutic target. © 2016 American Society for Bone and Mineral Research.

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Dynamic expression of Runx2, Osterix and AJ18 in the femoral head of steroid-induced osteonecrosis in rats

Abstract: Glucocorticoids may induce femoral head osteonecrosis by down-regulating Runx2/Osterix mRNA and up-regulating AJ18 mRNA.

Cited by 27 publications

References 14 publications

miR-27a attenuates adipogenesis and promotes osteogenesis in steroid-induced rat BMSCs by targeting PPARγ and GREM1

miR-27a attenuates adipogenesis and promotes osteogenesis in steroid-induced rat BMSCs by targeting PPARγ and GREM1

Cardioprotective effects of anisodamine against myocardial ischemia/reperfusion injury through the inhibition of oxidative stress, inflammation and apoptosis

TET3 Mediates Alterations in the Epigenetic Marker 5hmC and Akt pathway in Steroid-Associated Osteonecrosis

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