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      Long Noncoding RNA Zinc Finger Antisense 1 Affects Glucocorticoid-Induced Osteonecrosis of the Femoral Head by Performing as a ceRNA for MicroRNA-124-3p and Accelerating Transforming Growth Factor Type III Receptor


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          In recent years, plentiful studies have uncovered the long noncoding RNA's (lncRNA's) momentous functions in osteonecrosis of the femoral head (ONFH), but the specific mechanism has not been fully illustrated. The study was to figure out lncRNA Zinc finger antisense 1 (LncZFAS1)'s biological function and its latent downstream molecular mechanism in glucocorticoid- (GC-) induced ONFH. The results manifested LncZFAS1 and transforming growth factor type III receptor (TGFBR3) were elevated, while microRNA- (miR-) 124-3p was reduced in ONFH tissues and cells. Knockdown LncZFA1 reduced rat femoral cell apoptosis, perfected bone microstructure and bone density, and accelerated osteogenic proteins bone morphogenetic protein- (BMP-) 9, BMP-3, and osteocalcin. In vitro studies manifested knockdown LncZFAS1 prevented GC-induced reduction in osteoblast advancement with facilitating osteoblast calcification capacity, ALP activity, and osteogenic proteins. Elevation of LncZFAS1 further aggravated GC-induced osteoblast injury, but this effect was turned around by enhancement of miR-124-3p or knockdown of TGFBR3. Mechanistically, LncZFAS1 performed as a sponge for miR-124-3p to mediate TGFBR3 expression to motivate GC-induced ONFH. All in all, the results of this study indicate the LncZFAS1/miR-124-3p/TGFBR3 axis is supposed to be a latent therapeutic molecular target for GC-induced ONFH.

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          MicroRNAs (miRNAs) are small endogenous RNAs that regulate gene-expression posttranscriptionally. MiRNA research in allergy is expanding because miRNAs are crucial regulators of gene expression and promising candidates for biomarker development. MiRNA mimics and miRNA inhibitors currently in preclinical development have shown promise as novel therapeutic agents. Multiple technological platforms have been developed for miRNA isolation, miRNA quantitation, miRNA profiling, miRNA target detection, and modulating miRNA levels in vitro and in vivo. Here we will review the major technological platforms with consideration given for the advantages and disadvantages of each platform.
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            miR-542-3p suppresses osteoblast cell proliferation and differentiation, targets BMP-7 signaling and inhibits bone formation

            MicroRNAs (miRNAs) are short non-coding RNAs that interfere with translation of specific target mRNAs and thereby regulate diverse biological processes. Recent studies have suggested that miRNAs might have a role in osteoblast differentiation and bone formation. Here, we show that miR-542-3p, a well-characterized tumor suppressor whose downregulation is tightly associated with tumor progression via C-src-related oncogenic pathways, inhibits osteoblast proliferation and differentiation. miRNA array profiling in Medicarpin (a pterocarpan with proven bone-forming effects) induced mice calvarial osteoblast cells and further validation by quantitative real-time PCR revealed that miR-542-3p was downregulated during osteoblast differentiation. Over-expression of miR-542-3p inhibited osteoblast differentiation, whereas inhibition of miR-542-3p function by anti-miR-542-3p promoted expression of osteoblast-specific genes, alkaline phosphatase activity and matrix mineralization. Target prediction analysis tools and experimental validation by luciferase 3′ UTR reporter assay identified BMP-7 (bone morphogenetic protein 7) as a direct target of miR-542-3p. It was seen that over-expression of miR-542-3p leads to repression of BMP-7 and inhibition of BMP-7/PI3K- survivin signaling. This strongly suggests that miR-542-3p suppresses osteogenic differentiation and promotes osteoblast apoptosis by repressing BMP-7 and its downstream signaling. Furthermore, silencing of miR-542-3p led to increased bone formation, bone strength and improved trabecular microarchitecture in sham and ovariectomized (Ovx) mice. Although miR-542-3p is known to be a tumor repressor, we have identified second complementary function of miR-542-3p where it inhibits BMP-7-mediated osteogenesis. Our findings suggest that pharmacological inhibition of miR-542-3p by anti-miR-542-3p could represent a therapeutic strategy for enhancing bone formation in vivo.
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              Long non-coding RNA HOTAIR inhibits miR-17-5p to regulate osteogenic differentiation and proliferation in non-traumatic osteonecrosis of femoral head

              Background and aim The biological functions of non-coding RNAs (ncRNAs) have been widely identified in many human diseases. In the present study, the relationship between long non-coding RNA HOTAIR and microRNA-17-5p (miR-17-5p) and their roles in osteogenic differentiation and proliferation in non-traumatic osteonecrosis of femoral head (ONFH) were investigated. Methods The expression levels of HOTAIR and miR-17-5p in the mesenchymal stem cells (MSCs) derived from patients with non-traumatic ONFH and osteoarthritis (OA) were examined by real-time PCR. BMP-2 induced human MSCs from bone marrow (hMSC-BM) were used for osteogenic differentiation. Results It was observed that the expression level of miR-17-5p was lower and the level of HOTAIR was higher in samples of non-traumatic ONFH compared with OA. HOTAIR downregulation induced by si-HOTAIR led to the increase of miR-17-5p expression and the decrease of miR-17-5p target gene SMAD7 expression. The values of osteogenic differentiation markers, including RUNX2 and COL1A1 mRNA expression and ALP activity, were also elevated by si-HOTAIR. However, the increase of these values was canceled by miR-17-5p inhibitor or SMAD7 upregulation. Conclusion HOTAIR played a role in regulating osteogenic differentiation and proliferation through modulating miR-17-5p and its target gene SMAD7 in non-traumatic ONFH.

                Author and article information

                Comput Math Methods Med
                Comput Math Methods Med
                Computational and Mathematical Methods in Medicine
                18 July 2022
                : 2022
                : 4487864
                1Department of Rehabilitation Medicine, Second Affiliated Hospital of Nanchang University, Nanchang City, Jiangxi Province 330008, China
                2Department of Ultrasound (Musculoskeletal Ultrasound), Second Affiliated Hospital of Nanchang University, Nanchang City, Jiangxi Province 330008, China
                3Department of Nursing, Second Affiliated Hospital of Nanchang University, Nanchang City, Jiangxi Province 330008, China
                Author notes

                Academic Editor: Ahmed Faeq Hussein

                Author information
                Copyright © 2022 Xiao Yong Lan et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                : 20 May 2022
                : 15 June 2022
                : 16 June 2022
                Research Article

                Applied mathematics
                Applied mathematics


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