Gene Expression Profile of Steroid-induced Necrosis of Femoral Head of Rats

Abstract

The key to treating steroid-induced necrosis of femoral heads (SINFH) is early diagnosis. Dramatic improvements in diagnosis could be made if the pathogenesis of SINFH was more fully understood; however, the underlying mechanism of this disease is currently unknown. To explore the potential mechanism of SINFH, we performed gene array analysis on a rat model of the disease and compare the expression profile with that of normal rats. A quantitative RT-PCR and immunohistochemistry (IHC) assays were used to confirm the microarray results. Compared to the control group, 190 genes in the experimental group were differentially expressed, with 52 up-regulated and 138 down-regulated. Of these genes, 102 are known (deposited in GenBank), while 88 of them are unknown. The known genes can be divided into several families according to their biological functions, such as oxidative stress, apoptosis, signal transduction, angiogenesis, extracellular matrix, lipid metabolism, and transcription related genes. The results of quantitative RT-PCR and IHC were consistent with gene chip results. Our findings indicate that many genes involved in diverse signaling pathways were differentially expressed between SINFH rats and normal rats. Furthermore, our findings suggest that the development of SINFH is a complicated and dynamic process affected by multiple factors and signaling pathways and regulated by various genes.

Animal models of steroid-induced osteonecrosis of the femoral head—a comprehensive research review up to 2018

“…In recent years, many attempts to elucidate the genetic contributors to SONFH have been undertaken. Tong et al [53] performed gene array analysis on a rat model of SONFH, confirmed the microarray results by using a quantitative RT-PCR and immunohistochemistry (IHC) assays. In their SONFH group, 190 individual genes showed differential expression relative to healthy controls, with 52 being upregulated and 138 being downregulated.…”

Steroid-induced osteonecrosis of the femoral head reveals enhanced reactive oxygen species and hyperactive osteoclasts

“…High oxidative stress is thought to be associated with the development of various bone disorders, including osteoporosis [29,30], bone tumours [31], diabetic osteopenia [32], rheumatoid arthritis [33], and ankylosing spondylitis [34]. Recent evidence also indicated that ROS are involved in the pathogenesis of steroid-induced ONFH [20,21,35] and that approaches inhibiting oxidative stress exert potential therapeutic effects on ONFH [35][36][37]. To validate this, a ROS probe (DHE) was administrated on the rats prior to sacrifice, which is distributed via the circulation enabling the direct visualization of ROS in tissues as we previously described [18].…”

“…Our previous work has demonstrated that ROS levels are increased during estrogen deficiency-induced osteoporosis in mice, and that antioxidant agents are effective in inhibiting osteoclast activity and thus preventing bone loss [18]. ROS have also been implicated in the pathogenesis of ONFH, causing damage to blood vessels and osteoblastic cell lineages [19][20][21]. However, the underlying mechanisms by which ROS levels change and cause the activation of the osteoclasts in the context of steroid-induced ONFH remain poorly understood.…”

Regulatory effect of microRNA‐34a on osteogenesis and angiogenesis in glucocorticoid‐induced osteonecrosis of the femoral head

“…The 48 male adult rats were randomly distributed into three groups (12 in the control group, 24 in the Dex group, and 12 in the mir‐34a over‐expression lentivirus group). The rats in the Dex group were given two injections of lipopolysaccharide (LPS, 20 µg/kg, Sigma, MO) at an interval of 24 h, and then dexamethasone (40 mg/kg, Pfizer, NY) was injected into the gluteus muscle daily for 3 days, as described in a previous study . The animals in the lentivirus group received an extra intravenous injection of mir‐34a over‐expressing lentivirus at a dose of 1E + 8 TU (Genechem Co. Ltd, Shanghai, China) 1 day before LPS injection.…”