Long non‐coding RNA AC018926.2 regulates palmitic acid exposure‐compromised osteogenic potential of periodontal ligament stem cells via the ITGA2/FAK/AKT pathway

Abstract

Although obesity has been proposed as a risk factor for periodontitis, the influence of excessive fat accumulation on the development of periodontitis and periodontal recovery from disease remains largely unknown. This study investigated the cellular response of periodontal ligament stem cells (PDLSCs) to elevated levels of a specific fatty acid, namely, palmitic acid (PA). The mechanism by which PA exposure compromises the osteogenic potential of cells was also explored. It was found that exposure of PDLSCs to abundant PA led to decreased cell osteogenic differentiation. Given that long non‐coding RNAs (lncRNAs) play a key role in the stem cell response to adverse environmental stimuli, we screened the lncRNAs that were differentially expressed in PDLSCs following PA exposure using lncRNA microarray analysis, and AC018926.2 was identified as the lncRNA that was most sensitive to PA. Next, gain/loss‐of‐function studies illustrated that AC018926.2 was an important regulator in PA‐mediated osteogenic differentiation of PDLSCs. Mechanistically, AC018926.2 upregulated integrin α2 (ITGA2) expression and therefore activated ITGA2/FAK/AKT signalling. Further functional studies revealed that inactivation of ITGA2/FAK/AKT signalling by silencing ITGA2 counteracted the pro‐osteogenic effect induced by AC018926.2 overexpression. Moreover, the results of bioinformatics analysis and RNA immunoprecipitation assay suggested that AC018926.2 might transcriptionally regulate ITGA2 expression by binding to PARP1 protein. Our data suggest that AC018926.2 may serve as a therapeutic target for the management of periodontitis in obese patients.

Long non‐coding RNA LncTUG1 regulates favourable compression force‐induced cementocytes mineralization via PU.1/TLR4/SphK1 signalling

“…Since the regulatory roles of lncRNAs are associated with their subcellular localization, 30 we performed the FISH and subcellular fractionation assays illustrating that LncTUG1 was mainly distributed in the nuclear fraction (Figure 2A,B ), which suggested that LncTUG1 might regulate the transcription of targeted genes. 33 Based on this finding, we further investigated the downstream gene targeted by LncTUG1 during stress‐induced cementocyte mineralization.…”

“…An orthodontic closed coil spring (Grikin Advanced Materials, Beijing, China) was inserted between the maxillary left first molar (M1) and the incisor to achieve orthodontic molar movement with 0 g (Control group) and 25 g (Stress group). Stress was also combined with daily intraperitoneal injection of a TLR4‐specific agonist Lipopolysaccharide (LPS) (2 mg/kg, L2630, Millipore, Sigma‐Aldrich, St. Louis, MO, USA) 30 or with intraperitoneal injection of an SphK1 activator (0.05 mg/kg, K6PC‐5, Selleck, Beijing, China), 31 , 32 which were divided as Stress + LPS group and Stress + K6PC‐5 group, respectively. After 14 days, all experimental rats were euthanized by an overdose of pentobarbital and alveolar bone blocks that included M1 were harvested for further analysis.…”

“…The sequences of the primers used in the ChIP-PCR assays were listed in Table S3. Louis, MO, USA) 30 or with intraperitoneal injection of an SphK1 activator (0.05 mg/kg, K6PC-5, Selleck, Beijing, China), 31,32 which were divided as Stress + LPS group and Stress + K6PC-5 group, respectively. After 14 days, all experimental rats were euthanized by an overdose of pentobarbital and alveolar bone blocks that included M1 were harvested for further analysis.…”

Long Non-coding RNA-H19 Regulates Osteogenic Differentiation via microRNA-140-5p/Wnt1 Signaling in Bone Marrow Mesenchymal Stem Cells

“…Our previous study has found that the miRNA-140-5p expression decreased during osteogenic differentiation process of BMSCs, and BMSCs osteogenic differentiation is promoted by miRNA-140-5p down-regulation through targeting the Wnt l signal pathway [7] , however, the relative mechanism about miRNA-140-5p low expression in this process is still unclear. LncRNAs, as a miRNA molecular sponge, LncRNAs have increasingly been studied in relation to osteogenic differentiation [24][25][26][27][28] . The predicted results of Star base Database indicated that lncRNA-H19 may target the miRNA-140-5p.…”

Spore Oil-Functionalized Selenium Nanoparticles Protect Pancreatic Beta Cells from Palmitic Acid-Induced Apoptosis via Inhibition of Oxidative Stress-Mediated Apoptotic Pathways

“…However, the ability of pancreatic β-cells to resist oxidative stress is relatively weak, and oxidative stress induced by being in a high-fat state inevitably causes damage to the function and number of β-cells. Palmitic acid (PA), a saturated fatty acid [ 8 , 9 ] widely present in palm, vegetable, and catalpa oils, is the major component obtained from the daily diet that accumulates in the body, resulting in lipotoxicity of pancreatic β-cells.…”