Erratum: MicroRNA-125b-1-3p mediates intervertebral disc degeneration in rats by targeting teashirt zinc finger homeobox 3.

[This corrects the article DOI: 10.3892/etm.2018.5715.].

[Corrigendum] Overexpression of septin­7 inhibits melatonin­induced cell apoptosis in human fetal osteoblastic cells via suppression of endoplasmic reticulum stress.

Subsequently to the publication of this paper, an interested reader drew to the authors' attention that Figs. 2 and 4, featured on p. 4820 and 4821 respectively, contained apparently matching control ß­actin western blots. The authors have consulted their original data, and realized that the control western blot images were inadvertently selected incorrectly for Fig. 2. The corrected version of Fig. 2, showing the relevant ß­actin bands for Fig. 2, is shown on the next page. Note that the errors in Fig. 2 did not significantly affect the results or the conclusions reported in this paper, and all the authors agree to this Corrigendum. The authors are grateful to the Editor of Molecular Medicine Reports for allowing them the opportunity to publish this corrigendum, and apologize to the readership for any inconvenience caused. [the original article was published in Molecular Medicine Reports 17: 4817­4822, 2018; DOI: 10.3892/mmr.2018.8449].

Septin4 regulates endoplasmic reticulum stress and apoptosis in melatonin­induced osteoblasts.

Idiopathic scoliosis (IS) is a spinal 3­dimensional deformity with an unknown cause. Melatonin is secreted by the pineal body and contributes to the occurrence and progression of IS. In our previous preliminary study, it was reported that high concentrations of melatonin can induce osteoblast apoptosis, thus acting as an IS treatment, but the mechanism of action is unknown. Therefore, the present study was performed to further investigate the possible mechanism underlying the efficacy of melatonin as a treatment for IS. The present results indicated that high concentrations of melatonin mediate endoplasmic reticulum stress (ERS)­induced apoptosis in hFOB 1.19 cells, and this resulted in a significant and dose­dependent increase in the expression of Septin4, as well as the expression levels of glucose­regulated protein (GRP)78, GRP94 and cleaved caspase­3. Furthermore, osteoblasts were overexpressed with Septin4 and the mechanism via which melatonin induces osteoblast ERS was demonstrated to be via the regulation of Septin4. In addition, it was indicated that cytoskeleton destruction, cell morphology changes and the decrease in the number of cells were aggravated after osteoblasts were overexpressed with Septin4, as indicated by phalloidin and DAPI staining. Collectively, the present results suggest that the Septin4 protein may be a target of ERS in melatonin­induced osteoblast apoptosis, which is involved in bone metabolism diseases, thus providing novel evidence for clinical melatonin treatment of IS.

miR-590-3p mediates melatonin-induced cell apoptosis by targeting septin 7 in the human osteoblast cell line hFOB 1.19.

The present study aimed to investigate the association between septin 7 (SEPT7) and melatonin-induced apoptosis in the human fetal osteoblastic cell line hFOB 1.19. MicroRNA (miR)­590­3p was identified by identifying overlapping miRNAs that target SEPT7, across different databases (miRDB, DIANA and Targetscan). Apoptosis was assessed via flow cytometric analysis. Small interfering RNA of SEPT7 and a miR­590­3p inhibitor were used for gene silencing and the efficiency was assessed by reverse transcription­quantitative polymerase chain reaction. Western blotting was used to measure the expression of proteins associated with pathways mediating endoplasmic reticulum stress and melatonin­induced apoptosis. The present study identified that SEPT7 was a potential target of miR­590­3p and demonstrated that SEPT7 is associated with mediating the pro­apoptotic effect of miR­590­3p in human osteoblast cell line hFOB 1.19. High concentrations of melatonin may result in the inhibition of miR­590­3p expression, leading to the upregulation of target genes that promote apoptosis.

MicroRNA-125b-1-3p mediates intervertebral disc degeneration in rats by targeting teashirt zinc finger homeobox 3.

The present study aimed to investigate the association between Teashirt zinc finger homeobox 3 (TSHZ3) and the nucleus pulposus (NP) of intervertebral discs in rats. TSHZ3 was identified from the differentially expressed micro (mi)RNAs in the expression profile of GSE63492 by identifying the overlapped target genes of microRNA (miR)-125b-1-3p across different databases. TSHZ3 small interfering RNA (siRNA) and an miR-125b-1-3p inhibitor were used for gene silencing and gene silencing efficiency was assessed by reverse transcription-polymerase chain reaction. Western blotting was performed to detect the cell cycle proteins cyclin D1 and B1 and the proteins associated with DNA damage in NP. The results revealed that in normal NPs, the expression of TSHZ3 increased following the inhibition of miR-125b-1-3p and in DNA damaged NPs, the expression of TSHZ3 was associated with the degree of DNA damage. The present study demonstrated that TSHZ3, as a target gene of miR-125b-1-3p, may serve a protective role in intervertebral disc degeneration and that this protective function may be inhibited by high levels of miR-125b-1-3p.

Septin4 as a novel binding partner of PARP1 contributes to oxidative stress induced human umbilical vein endothelial cells injure.

Oxidative stress induced vascular endothelial cell injure is one of the key and initial event in the development of atherosclerosis. Septin4, as a member of GTP binding protein family, is widely expressed in the eukaryotic cells and considered to be an essential component of the cytoskeleton which is involved in many important physiological processes. However, whether Septin4 is involved in cardiovascular diseases, such as oxidative stress inducted endothelial cell injury still unclear. PARP1 as a DNA repair enzyme can be activated by identifying DNA damaged fragments, which consumes high levels of energy and leads to vascular endothelial cell apoptosis. Here, our results first found that Septin4 is involved in oxidative stress induced endothelial cell ROS production and apoptosis through knock-down and over-expression Septin4 approaches. Furthermore, to explore how Septin4 is involved in oxidative stress induced endothelial cells injure, we first identified that Septin4 is a novel PARP1 interacting protein and the interaction is enhanced under oxidative stress. In conclusions, our founding indicates that Septin4 is a novel essential factor involved in oxidative stress induced vascular endothelial cell injury by interacting with apoptosis-related protein PARP1.

Overexpression of septin-7 inhibits melatonin-induced cell apoptosis in human fetal osteoblastic cells via suppression of endoplasmic reticulum stress.

Our previous study demonstrated that melatonin could induce apoptosis in the human fetal osteoblastic (hFOB) 1.19 cell line via induction of endoplasmic reticulum stress (ERS), and recent studies have demonstrated that the expression of septin­7 (SEPT7) exhibits a positive correlation with the concentration of melatonin. Western blotting demonstrated the expression level of SEPT7 was significantly upregulated in a dose­dependent manner following treatment with differing concentrations of melatonin compared with the control groups, which did not receive any treatment. The expression of proteins associated with cell apoptosis and endoplasmic reticulum stress (ERS; pro-caspase­3, cleaved caspase­3, C/EBP­homologous protein, 78 kDa glucose­regulated protein and phosphorylated­eukaryotic translation initiation factor 2α) were decreased following transfection with SEPT7 overexpression plasmid and increased following transfection with SEPT7 small interfering RNA compared with the control groups. The results of the present study suggest that SEPT7 inhibits melatonin­induced cell apoptosis via suppression of ERS.

Periostin has a protective role in melatonin­induced cell apoptosis by inhibiting the eIF2α­ATF4 pathway in human osteoblasts.

The present study aimed to investigate the role of periostin (POSTN) and high melatonin concentrations in the apoptosis of hFOB 1.19 human normal fetal osteoblastic cells. hFOB 1.19 human osteoblastic cells were stably cultured and treated in different concentrations of melatonin for different durations of action. Apoptosis was assessed quantitatively using flow cytometric analysis. The results of western blot analysis demonstrated that the treatment of cells with different concentrations of melatonin for different durations of action revealed a positive association between melatonin and the expression levels of glucose­regulated protein (GRP)78, GRP94, phosphorylated (p­) eukaryotic initiation factor 2α (eIF2α), activating transcription factor (ATF)4, CCAAT/enhanced binding protein homologous protein (CHOP), cleaved caspase­3, p­c­Jun N­terminal kinase (JNK) and POSTN. When POSTN was inhibited, the levels of p­JNK, CHOP, p­eIF2α, ATF4 and cleaved caspase­3 were significantly increased, whereas other proteins associated with the endoplasmic reticulum stress (ERS) pathways, including ATF6 and X­box binding protein 1 (XBP1), were not significantly altered. Reverse transcription­quantitative polymerase chain reaction analysis was also performed to assess the relative mRNA levels of ATF4, ATF6 and XBP1. The results of the present study are the first, to the best of our knowledge, to demonstrate that melatonin induced apoptosis in hFOB 1.19 human osteoblastic cells by activating the ERS­associated eIF2α­ATF4 pathway and subsequently triggered the cascade effects of CHOP, caspase­3 and JNK. POSTN may function as a protective factor for osteoblasts during this process by inhibiting the eIF2α­ATF4 pathway.