[Retracted] In vitro antitumor activity of the ethyl acetate extract Potentilla chinensis in osteosarcoma cancer cells.

Following the publication of the above paper, a concerned reader drew to the Editor's attention that several figures bore striking similarities to other papers that were published at around the same time written by different authors based in different research institutions. Fig. 3 (in colour) was essentially the same as a greyscale figure (Fig. 4) in a paper published in Oncology Reports, which has now been retracted [Wan G, Tao J­G, Wang G­D, Liu S­P, Zhao H­X and Liang Q­D: 3­ß­Εrythrodiol isolated from Conyza canadensis inhibits MKN­45 human gastric cancer cell proliferation by inducing apoptosis, cell cycle arrest, DNA fragmentation, ROS generation and reduces tumor weight and volume in mouse xenograft mode. Oncol Rep 35: 2328­2338, 2016]. Furthermore, Figs. 5 and 6 in the above paper appeared to share data with Figs. 7 and 11, respectively, in a paper published in Phytomedicine [Sui C­G, Meng F­D and Jiang Y­h: Antiproliferative activity of rosamultic acid is associated with induction of apoptosis, cell cycle arrest, inhibition of cell migration and caspase activation in human gastric cancer (SGC­7901) cells. Phyomedicine 22: 796­806, 2015]. After having conducted an independent investigation in the Editorial Office, the Editor of Molecular Medicine Reports has determined that the above paper should be retracted from the Journal on account of a lack of confidence concerning the originality and the authenticity of the data. The authors were asked for an explanation to account for these concerns, but the Editorial Office never received any reply. The Editor regrets any inconvenience that has been caused to the readership of the Journal. [the original article was published in Molecular Medicine Reports 14: 3634­3640, 2016; DOI: 10.3892/mmr.2016.5679].

Down-regulation of microRNA-203a suppresses IL-1ß-induced inflammation and cartilage degradation in human chondrocytes through Smad3 signaling.

Osteoarthritis (OA) is a chronic and prevalent degenerative musculoskeletal disorder, which is characterized by articular cartilage degradation and joint inflammation. MicroRNA-203a (miR-203a) has been shown to be involved in multiple pathological processes during OA, but little is known about its function in chondrocyte extracellular matrix (ECM) degradation. In the present study, we aimed to elucidate the effects of miR-203a on articular cartilage degradation and joint inflammation. We observed that the miR-203a level was significantly up-regulated in OA tissues and in an in vitro model of OA, respectively. Inhibition of miR-203a significantly alleviated the interleukin (IL)-1ß-induced inflammatory response and ECM degradation in chondrocytes. Moreover, mothers against decapentaplegic homolog 3 (Smad3), a key factor in maintaining chondrocyte homeostasis, was identified as a putative target of miR-203a in chondrocytes. More importantly, inhibition of Smad3 impaired the inhibitory effects of the miR-203a on IL-1ß-induced inflammatory response and ECM degradation. Collectively, these results demonstrated that miR-203a may contribute to articular cartilage degradation of OA by targeting Smad3, suggesting a novel therapeutic target for the treatment of OA.

MicroRNA-129-5p alleviates spinal cord injury in mice via suppressing the apoptosis and inflammatory response through HMGB1/TLR4/NF-κB pathway.

Secondary injury after spinal cord injury (SCI) is one reversible pathological change mainly involving excessive inflammatory response and neuro-apoptosis. Since in recent years, microRNAs (miRNAs) have been proposed as novel regulators of inflammation in different disease conditions. However, the role of miRNAs in the inflammatory response and apoptosis of secondary injury after SCI remains to be fully elucidated. Here, we tried to explore the influence and mechanism of miRNAs on the neuron inflammatory response and apoptosis after SCI. The expression profiles of miRNA were examined using miRNA microarray, and among the candidate miRNAs, miR-129-5p was found to be the most down-regulated miRNA in spinal tissues. Overexpression of miR-129-5p using agomir-miR-129-5p promoted injury mice functional recovery, suppressed the apoptosis and alleviated inflammatory response in spinal tissues. Using LPS-induced BV-2 cell model, we found miR-129-5p was also proved in protecting inflammatory response and cell apoptosis in vitro. High-mobility group protein B1 (HMGB1), a well-known inflammatory mediator, was found to be directly targeted by miR-129-5p and it was associated with the inhibitory effect of miR-129-5p on the activation of toll-like receptor (TLR)-4 (TLR4)/ nuclear factor-κB (NF-κB) pathway in vitro and in vivo. Further experiments revealed that the anti-apoptosis and anti-inflammatory effects of miR-129-5p were reversed by HMGB1 overexpression in BV-2 cells. Collectively, these data revealed that miR-129-5p alleviated SCI in mice via suppressing the apoptosis and inflammatory response through HMGB1//TLR4/NF-κB pathway. Our data suggest that up-regulation of miR-129-5p may be a novel therapeutic target for SCI.

C1q/TNF-related protein-3 exerts the chondroprotective effects in IL-1ß-treated SW1353 cells by regulating the FGFR1 signaling.

Cartilage degeneration is known as a major cause of osteoarthritis (OA). C1q/TNF-related protein-3 (CTRP3) is an adipokine relative to chondrogenesis in vitro. However, its effect on cartilage degeneration in OA remains unclearly. In the present study, SW1353 cells were treated with IL-1ß to imitate the microenvironment of OA for vitro research. Then, an obvious down-regulation of CTRP3 were validated in IL-1ß-treated SW1353 cells. In addition, CTRP3 overexpression significantly attenuated the decrease in cell proliferation and increase in cell apoptosis triggered by IL-1ß. Moreover, CTRP3 up-regulation significantly inhibited the expression of FGFR1, but with slight decrease in FGFR3 levels. Further analysis corroborated that FGFR1 overexpression markedly ameliorated the pro-proliferation and anti-apoptotic effects of CTRP3 elevation in cells upon IL-1ß. Down-regulation of FGFR1 attenuated the increase in Ras-GTP expression caused by IL-1ß stimulation. Moreover, EGFR1 elevation also abated the inhibitory effect of CTRP3 on Ras expression and the CRTP3-induced activation of PI3K/AKT in cells upon IL-1ß. Furthermore, Ras inhibitor manumycin A antagonized the decrease in phosphorylation of PI3K and Akt caused by IL-1ß treatment. Both Manumycin A and PI3K/Akt agonist FGF-1 attenuated the inhibitory effect of IL-1ß on cell growth. Together, this research suggested that CTRP3 might protect chondrocytes against IL-1ß-induced injury by suppressing the FGFR1- Ras/PI3K/Akt signaling-mediated growth inhibitory pathway, indicating a potential agent against osteoarthritis.

ST1926 Attenuates Steroid-Induced Osteoporosis in Rats by Inhibiting Inflammation Response.

Steroid, also known as glucocorticoid, induced osteonecrosis of the femoral head in young adults, which has been a challenging disorder for the frequent incidence of collapse of femoral head, leading to dysfunction of hip joint and impairing life quality of human. Bioavailable and less toxic synthetic retinoids, such as the atypical adamantyl retinoid ST1926, have been developed and investigated in clinical trials for many diseases. Serum lipid-related indicators were assessed to elucidate the role of ST1926 in regulating lipid metabolism. Microfocal computed tomography (Micro-CT) was included to explore the effects of ST1926 treatment on microstructure and bone mass. Then, the role of ST1926 treatment in regulating osteoclast differentiation was also evaluated in vivo and in vitro. In addition, alkaline phosphatase (ALP), osteoprotegerin (OPG), bone alkaline phosphatase (BAP) and bone morphogenic protein (BMP) expression in serum and cells were detected at protein or mRNA levels. The ratio of empty lacuna in the bone tissue samples was significantly low in ST1926-treated groups than in the control group. Micro-CT evaluation suggested that ST1926 treatment could ameliorate the microstructure of the bone and up-regulate bone mineral density in steroid-induced rats. Moreover, ST1926 treatment suppressed osteoclast differentiation and promoted bone formation markers. Also, OPG, ALP, and Wnt3a/ß-catenin down-regulation as well as inflammation up-regulation could be reversed by ST1926 administration through NFκB inhibition. Hence, ST1926 may inhibit steroid-induced osteoporosis and promote steroid-induced bone remodeling by regulating the Wnt3a/ß-catenin/NFκB signaling pathway. J. Cell. Biochem. 118: 2072-2086, 2017. © 2017 Wiley Periodicals, Inc.

Upregulation of lncRNA HNF1A-AS1 promotes cell proliferation and metastasis in osteosarcoma through activation of the Wnt/ß-catenin signaling pathway.

HNF1A-antisense 1 (HNF1A-AS1), a long non-coding RNA (lncRNA), is associated with metastasis and is an independent prognostic factor for lung cancer. Recent studies demonstrated that HNF1A-AS1 play important roles in cacinogenesis. However, the exact effects and molecular mechanisms of HNF1A-AS1 in osteosarcoma (OS) progression is still unclear. In the present study, we found that HNF1A-AS1 was markedly up-regulated in OS tissues compared to their adjacent non-tumor tissues. HNF1A-AS1 expression levels were positively associated with the clinical stage, distant metastasis, and reduced overall survival of OS patients. In addition, knockdown HNF1A-AS1 expression inhibited cell proliferation, metastasis and influences the activity of the Wnt/ß-catenin pathway in OS cells. Wnt/ß-catenin pathway activator (LiCl) rescued the anticancer effect of knockdown HNF1A-AS1 expression in OS cells. In conclusion, our study demonstrated that HNF1A-AS1 promoted the progression of OS via regulating the activity of the Wnt/ß-catenin pathway, indicating that HNF1A-AS1 might be a potential target for the treatment of OS.

In vitro antitumor activity of the ethyl acetate extract of Potentilla chinensis in osteosarcoma cancer cells.

The aim of the current study was to evaluate the anticancer effect of the ethanol extract of Potentilla chinensis, a Chinese medicinal plant. An MTT assay was used to evaluate the cell viability of MG­63 human osteosarcoma cancer cells and fR­2 cells. Furthermore, the effect of the extract on apoptosis induction, cell cycle phase distribution and inhibition of cell migration in the MG63 human osteosarcoma cancer cell line was evaluated. The effect of the extract on cell cycle phase distribution was assessed by flow cytometry using propidium iodide (PI). Phase contrast microscopy detected the morphological changes in MG63 cancer cells following extract treatment. The results of the study demonstrated that the extract was cytotoxic to MG63 cancer cells, while the normal cell line (epithelial cell line) showed lower susceptibility. Phase contrast microscopy showed distinguishing morphological features, such as cell shrinkage and blebbing induced by the extract treatment in osteosarcoma cancer cells. The average proportion of Annexin V­positive cells (total apoptotic cells) significantly increased from 5.6% in the control to 24.2, 38.8 and 55.7% in the 40, 80 and 150 µg/ml groups, respectively. The extract induced early and late apoptosis in the cancer cells. Flow cytometric analysis revealed that the extract induced G0/G1­cell cycle arrest, which also showed significant dose­dependence. The extract induced a significant and concentration­dependent reduction in cell migration. Moreover, DNA fragmentation was also examined by observation of the formation of DNA ladders. It was demonstrated that DNA fragmentation was increased with extract concentration compared with that in the control. Taken together, EEPC may serve as potential therapeutic agent against osteosarcoma, provided that the toxicity profile and in vivo investigations demonstrate that it is safe.

Elevated serum levels of Interleukin-37 are associated with inflammatory cytokines and disease activity in rheumatoid arthritis.

Interleukin-37 (IL-37) is closely associated with several inflammatory diseases. However, the role of IL-37 in the pathogenesis of rheumatoid arthritis (RA) remains unclear. The aim of this study was to assess the associations between serum levels of IL-37 and disease activity, inflammatory cytokines, and bone loss in patients with RA. Serum cytokines levels were examined by Enzyme-linked immunosorbent assay (ELISA). Radiographic bone erosion was assessed using the van der Heijde-modified Sharp score and bone mineral density (BMD) was measured using DXA. Serum IL-37 levels in RA patients were significantly higher than those in HCs (p < 0.001), and were significantly positively correlated with clinical parameters of disease activity and serum levels of IL-17 and IL-23. In addition, serum IL-37 levels were significantly higher in patients with stage IV of radiographic bone erosion than those with stage III and stage I-II, and they were significantly higher in those with osteopenia and osteoporosis than in those with normal BMD. Our results suggest that serum IL-37 levels were increased in patients with RA and were positively associated with disease activity, IL-17/IL-23 and bone loss in RA, suggesting that IL-37 may play a critical role in the pathogenesis of RA.