Risk of New Vertebral Fracture and Combination Therapy with Zoledronic Acid and Teriparatide in Diabetic Patients after Percutaneous Kyphoplasty

Zhang Jian,Yan Bin,Chen Zhe,Zheng Zhaomin,Yang Changsheng 대한척추외과학회 2021 Asian Spine Journal Vol.15 No.5

Study Design: This was a retrospective clinical study. Purpose: This study aimed to evaluate the effect of combination therapy with zoledronic acid and teriparatide on the risk of new vertebral fracture (NVF) in type 2 diabetes mellitus (T2DM) patients after percutaneous kyphoplasty (PKP). Overview of Literature: Although T2DM had been associated with bone fragility and increased fracture risk, it remains unknown whether patients with T2DM could expect similar benefit from the combination therapy with zoledronic acid and teriparatide following PKP. Methods: Total 106 diabetic patients who had undergone PKP and had received anti-osteoporosis treatment for osteoporotic vertebral compression fracture were enrolled and allocated into the following two groups: group I (n=52, zoledronic acid) and group II (n=54, zoledronic acid plus teriparatide). The operating time, bone cement volume, and complications related to anti-osteoporosis treatment or PKP, if any, were recorded. The Visual Analog Scale (VAS) score and Oswestry Disability Index (ODI) were assessed at admission, at discharge, and at the final follow-up. Dual-energy X-ray absorptiometry scan of the hip for the measurement of the bone mineral density (BMD) was performed preoperatively and at the final follow-up for all the patients. Results: There was no significant difference in the age, body mass index, bone cement volume, or follow-up time of the groups. The mean follow-up duration was 22.5±1.6 months. All the patients had improved VAS and ODI, and group II had significantly better clinical outcomes than group I. All the patients had increased BMD at the latest follow-up, while group II exhibited significantly more improvement. The prevalence of NVF was lower in group II (11.5% vs. 7.4%, p=0.523). Male patients had a higher prevalence of NVF although the difference was not statistically significant. Conclusions: Combination therapy with zoledronic acid and teriparatide could improve the clinical outcomes, and BMD and had the potential to reduce NVF in diabetic patients following PKP.

Circular RNA circ-4099 is induced by TNF-α and regulates ECM synthesis by blocking miR-616-5p inhibition of Sox9 in intervertebral disc degeneration

Hua Wang,Peiheng He,Hehai Pan,Jun long,Jianru Wang,Zemin Li,Hui Liu,Weiying Jiang,Zhaomin Zheng 생화학분자생물학회 2018 Experimental and molecular medicine Vol.50 No.-

Circular RNAs (circRNAs) play important roles in the initiation and development of different diseases. Here, we detected their role in intervertebral disc (IVD) degeneration. An Arraystar human circular RNA microarray assay was used to detect circRNAs in normal and degenerated human IVD nucleus pulposus (NP) tissues. The role of circ-4099 in IVDD and its mechanism were evaluated by qRT-PCR and gain-of-function/loss-of-function studies. Interaction networks for competing endogenous RNAs (ceRNAs), miRNAs, and miRNA target gene were detected by bioinformatics analysis, RNA immunoprecipitation and luciferase assay. Expression of seventy-two circRNAs were increased by more than twofold in degenerated NP tissues. qRT-PCR showed that the expression of circ-4099 in NP tissues was consistent with that of the array screening. Over-expression of circ-4099 increased the expression of Collagen II and Aggrecan and decreased the secretion of the pro-inflammatory factors IL-1β, TNF-α, and PGE2. TNF-α treatment increased circ-4099 expression in NP cells. NF-κB/MAPK inhibitors or shRNAs abolished the inductive effects of TNF-α on circ-4099 expression. We further demonstrated that circ-4099 was able to function as a “sponge” by competitively binding miR-616-5p, which reversed the suppression of Sox9 by miR-616-5p. We used DNA pull-down and spectrometry experiments to show that TNF-α can promote circ-4099 transcription through upregulation of GRP78. We provide the first evidence that shows circRNAs are differentially expressed in degenerated and normal NP tissues. Circ-4099 may play a role in a protective mechanism and be part of a compensatory response that maintains the synthesis and secretion of the extracellular matrix in NP cells and might be a protective factor in IVD degeneration as well as restore NP cell function.

Risk Factors Associated with Pain Severity in Patients with Non-specific Low Back Pain in Southern China

Shilabant Sen Sribastav,Jun Long,Peiheng He,Wei He,Fubiao Ye,Zemin Li,Jianru Wang,Hui Liu,Hua Wang,Zhaomin Zheng 대한척추외과학회 2018 Asian Spine Journal Vol.12 No.3

Study Design: A prospective cross-sectional study. Purpose: To evaluate the risk factors associated with the severity of pain intensity in patients with non-specific low back pain (NSLBP) in Southern China. Overview of Literature: Low back pain (LBP) is the leading cause of activity limitation and work absence throughout the world, so a firm understanding of the risk factor associated with NSLBP can provide early and prompt interventions that are aimed at attaining long-term results. Methods: Participants were recruited from January 2014 to January 2016 and were surveyed using a self-designed questionnaire. Anonymous assessments included Short Form 36-Item Health Survey (SF-36) and Visual Analogue Scale (VAS). The association between the severity of NSLBP and these potential risk factors were evaluated. Results: A total of 1,046 NSLBP patients were enrolled. The patients with primary school education, high body mass index (BMI), those exposed to sustained durations of driving and sitting, smoking, recurrent LBP had increased VAS and Oswestry Disability Index (ODI) scores with lower SF-36 scores (p <0.01). Workers and drivers compared with waiters and patients who lifted >10 kg objects in a quarter of their work time for >10 years had higher VAS and ODI scores with lower SF-36 scores (p <0.01). Multiple logistic regression showed lower levels of education, LBP for 1–7 days, long-lasting LBP in last year, smoking, long duration driving, and higher BMI were associated with more severe VAS score. Conclusions: The severity of NSLBP is associated with lower levels of education, poor standards of living, heavy physical labor, long duration driving, and sedentary lifestyle. Patients with recurrent NSLBP have more severe pain. Reducing rates of obesity, the duration of heavy physical work, driving or riding, and attenuating the prevalence of sedentary lifestyles and smoking may reduce the prevalence of NSLBP.

TGF-β1 suppresses CCL3/4 expression through the ERK signaling pathway and inhibits intervertebral disc degeneration and inflammation-related pain in a rat model

Jian Zhang,Zemin Li,Fan Chen,Hui Liu,Hua Wang,Xiang Li,Xianguo Liu,Jianru Wang,Zhaomin Zheng 생화학분자생물학회 2017 Experimental and molecular medicine Vol.49 No.-

The objective of this study was to investigate the regulatory effects of TGF-β1 on CCL3/4 expression and inflammation-related pain during intervertebral disc degeneration (IVDD). TGF-β1 and CCL3/4 expression patterns in different degenerative human nucleus pulposus (NP) tissues were measured by qPCR and immunohistochemistry (IHC), and the effects of TGF-β1 on CCL3/4 expression were measured by qPCR, ELISA and immunofluorescence. The roles of NF-κB and MAPK in TGF-β1-mediated CCL3/4 promoter activity were studied using siRNAs, western blotting and qPCR. After establishing an IVDD rat model in vivo, we administered intradiscal injections of TGF-β1. The effects of TGF-β1 on IVDD were determined by MRI and histological analyses, and the effects of TGF-β1 on dorsal root ganglion (DRG) inflammation and pain development were determined by IHC staining and pain-behavior testing, respectively. TGF-β1 and CCL3/4 expression was elevated in degenerative NP tissue. CCL4 expression was significantly inhibited by TGF-β1 treatment. Pharmacological inhibition or siRNA knockdown of the ERK1/2 signaling attenuated TGF-β1-mediated suppression of CCL4 expression. In vivo, TGF-β1 injection inhibited the development of degenerative features in the IVDD model. Moreover, TGF-β1 prevented the inflammatory response and pain development. The results of this study show that TGF-β1 downregulates CCL4 expression through ERK1/2 signaling activation in NP cells. Furthermore, TGF-β1 can prevent degenerative processes, inhibit inflammatory responses in the DRG and prevent pain development in the IVDD rat model. The results of this study indicate that TGF-β1 may represent a therapeutic target for the control of inflammation-related pain associated with IVDD.

Grem1 accelerates nucleus pulposus cell apoptosis and intervertebral disc degeneration by inhibiting TGF-β-mediated Smad2/3 phosphorylation

Chen Shunlun,Lei Linchuan,Li Zemin,Chen Fan,Huang Yuming,Jiang Guowei,Guo Xingyu,Zhao Zhuoyang,Liu Hui,Wang Hua,Liu Caijun,Zheng Zhaomin,Wang Jianru 생화학분자생물학회 2022 Experimental and molecular medicine Vol.54 No.-

Intervertebral disc degeneration (IVDD) is a main cause of low back pain, and inflammatory factors play key roles in its pathogenesis. Gremlin-1 (Grem1) was reported to induce an inflammatory response in other fields. This study aimed to investigate the mechanisms of Grem1 in the degenerative process of intervertebral discs. Dysregulated genes were determined by analyzing microarray profiles. The expression of Grem1 in 17 human disc samples (male:female = 9:8) and rat models (n = 5 each group) was measured by western blotting (WB), real-time quantitative PCR (RT-qPCR), and immunohistochemistry (IHC). The regulatory effects of Grem1 on apoptosis were examined using siRNAs, flow cytometry, immunofluorescence (IF), and WB. The therapeutic effect was evaluated by locally injecting specific Grem1 siRNA into IVDD rats. The expression of Grem1 was significantly increased in human degenerative intervertebral discs; furthermore, the expression of Grem1 positively correlated with the level of intervertebral disc degeneration. Grem1 was significantly overexpressed in tumor necrosis factor (TNF)-α-induced degenerative NP cells. Apoptosis in degenerative NP cells transfected with siRNA targeting Grem1 was significantly lower than that in the control group. Specific Grem1 siRNA markedly repressed the development of IVDD in surgery-induced IVDD rats. These results indicated that the expression of Grem1 was positively correlated with the severity of intervertebral disc degeneration, and Grem1 siRNA could inhibit Grem1-induced apoptosis and extracellular matrix alterations by mediating the TGF-β/Smad signaling pathway. This study may provide a therapeutic strategy for alleviating inflammation-induced apoptosis associated with intervertebral disc degeneration.