Osteoarthritis (OA) is characterized by progressive destruction of articular cartilage, resulting in significant disability. Inflammatory cytokines commonly initiate the extreme changes in the synovium and cartilage microenvironment of the OA patients, subsequently resulting in cell dysfunctions, especially synoviocyte dysfunction. We revealed that the expression of osteopontin (OPN), which has been reported to regulate expression of various inflammatory factors associating with the pathogenesis of OA including matrix metalloprotease 13 (MMP13), interlukine-6 and 8 (IL-6 and IL-8), is significantly upregulated in OA tissues. In the present study, online tools were used to screen out the candidate miRNAs of OPN. Among the candidate miRNAs, miR-181c inhibited OPN mRNA expression the most strongly. Ectopic expression of miR-181c significantly repressed synoviocyte proliferation, as well as the levels of OPN, MMP13, IL-6, and IL-8. Further, the candidate lncRNAs of miR-181c were screened out by using DianaTools; among which NEAT1 showed to inversely regulate miR-181c. By performing Luciferase assays, we revealed that NEAT1 competed with OPN for miR-181c binding. After NEAT1 knockdown, MMP13, IL-6, and IL-8 expression was reduced; the synoviocyte proliferation was repressed, as well as OPN protein levels; the suppressive effect of NETA1 knockdown on synoviocyte proliferation and the indicated factors were partially reversed by miR-181c inhibition. In OA tissues, OPN mRNA, and NEAT1 expression was upregulated, whereas miR-181c expression was downregulated, indicating that targeting NEAT1 to rescue miR-181c expression so as to inhibit OPN expression and synoviocyte proliferation might be an efficient strategy for OA treatment. J. Cell. Biochem. 118: 3775-3784, 2017. © 2017 Wiley Periodicals, Inc.

Background and Aims. A growing body of research has demonstrated that the degeneration of chondrocytes is the primary cause of osteoarthritis (OA). Parathyroid hormone-related protein (PTHrP) can alleviate the degeneration of chondrocytes via promotion of chondrocyte proliferation and inhibition of terminal differentiation, but the underlying mechanism remains unknown. This study aimed to identify the microRNAs (miRNAs) that may target PTHrP and regulate the proliferation and terminal differentiation of chondrocytes. Methods. Bioinformatic analysis was used to predict which miRNAs target PTHrP. We collected human knee cartilage specimens to acquire the primary chondrocytes, which we then used to test the expression and function of the targeted miRNAs. To explore the effects of miR-15a-5p on the putative binding sites, specific mimics or inhibitors were transfected into the chondrocytes. Furthermore, a dual-luciferase reporter gene assay and chondrocyte degeneration-related factors were used to verify the possible mechanism. Results. The expression of PTHrP was upregulated in the OA chondrocytes, whilst miR-15a-5p was downregulated in the OA chondrocytes. A negative correlation was observed between PTHrP and miR-15a-5p. The knockdown of miR-15a-5p promoted the growth of chondrocytes and inhibited calcium deposition, whilst overexpression of miR-15a-5p reversed this trend. The effect of miR-15a-5p overexpression was neutralised by PTHrP. Dual-luciferase reporter assays revealed that PTHrP can be used as a novel targeting molecule for miR-15a-5p. Conclusions. miR-15a-5p promotes the degeneration of chondrocytes by targeting PTHrP and, in addition to helping us understand the development of OA, may be a potential biomarker of OA.

Budding Uninhibited By Benzimidazoles are a group of genes encoding proteins that play central roles in spindle checkpoint during mitosis. Improper mitosis may lead to aneuploidy which is found in many types of tumors. As a key mediator in mitosis, the dysregulated expression of BUBs has been proven to be highly associated with various malignancies, such as leukemia, gastric cancer, breast cancer, and liver cancer. However, bioinformatic analysis has not been applied to explore the role of the BUBs in sarcomas. Herein, we investigate the transcriptional and survival data of BUBs in patients with sarcomas using Oncomine, Gene Expression Profiling Interactive Analysis, Cancer Cell Line Encyclopedia, Kaplan-Meier Plotter, LinkedOmics, and the Database for Annotation, Visualization and Integrated Discovery. We found that the expression levels of BUB1, BUB1B and BUB3 were higher in sarcoma samples and cell lines than in normal controls. Survival analysis revealed that the higher expression levels of BUB1, BUB1B and BUB3 were associated with lower overall and disease-free survival in patients with sarcomas. This study implies that BUB1, BUB1B and BUB3 are potential treatment targets for patients with sarcomas and are new biomarkers for the prognosis of sarcomas.

Rotator cuff injuries increase with age. The enthesis is the most frequent site of rotator cuff injury and degeneration. Understanding age‐related changes of the enthesis are essential to determine the mechanism of rotator cuff injuries, degeneration, and to guide mechanistically driven therapies. In this study, we explored age‐related cellular changes of the rotator cuff enthesis in young, mature, and aged rats. Here we found that the aged enthesis is typified by an increased mineralized zone and decreased nonmineralized zone. Proliferation, migration, and colony‐forming potential of rotator cuff derived cells (RCECs) was attenuated with aging. The tenogenic and chondrogenic potential were significantly reduced, while the osteogenic potential increased in aged RCECs. The adipogenic potential increased in RCECs with age. This study explores the cellular differences found between young, mature, and aged rotator cuff enthesis cells and highlights the importance of using age‐appropriate models, as well as provides a basis for further delineation of mechanisms and potential therapeutics for rotator cuff injuries.

Aim: This study was to detect the effects of purified exosome product (PEP) on C28/I2 cells and chondrocytes derived from osteoarthritis patients. Materials & methods: Cell viability and apoptosis assays were used to detect the effect of PEP on cells. qRT-PCR and cell fluorescence assays were used to investigate the potential mechanism of PEP on cell chondrogenesis. Results: PEP was internalized by cells at a fast rate and enhanced cellular proliferation and migration while attenuating apoptosis. These findings reflect the fact that PEP can increase the expression of  PCNA and reduce the expression of CASP3/ 7/ 9 and BAX. Conclusion: This study suggests an innovative strategy for chondrogenesis that could be applied to osteoarthritis repair in the future.

Objective. Most guidelines recommend the use of nonsteroidal anti-inflammatory drugs (NSAIDs), duloxetine, and tramadol for the nonoperative treatment of osteoarthritis (OA), but the use of them is limited by the tolerability and safety concerns. Lutikizumab is a novel anti–IL-1α/β dual variable domain immunoglobulin that can simultaneously bind and inhibit IL-1α and IL-1β to relieve the pain and dysfunction symptoms. We conducted this network meta-analysis to comprehensively compare the clinical efficacy and safety of lutikizumab with other drugs recommended by guidelines. Methods. We conducted a Bayesian network and conventional meta-analyses to compare the efficacy and safety of lutikizumab with other traditional drugs. All eligible randomized clinical trials, in PubMed, CNKI, EMBASE, and Web of Science databases, from January 2000 to January 2020, were included. The Cochrane risk of the bias assessment tool was used for quality assessment. Pain relief, function improvement, and risk of adverse effects (AEs) were compared in this study. Results. 24 articles with 11858 patients were included. Duloxetine (DUL) had the largest effect for pain relief (4.76, 95% CI [2.35 to 7.17]), and selective cox-2 inhibitors (SCI) were the most efficacious treatment for physical function improvement (SMD 3.94, 95% CI [2.48 to 5.40]). Lutikizumab showed no benefit compared with placebo for both pain relief (SMD 1.11, 95% CI [-2.29 to 4.52]) and function improvement (SMD 0.992, 95% CI [-0.433 to 4.25]). Lutikizumab and all other drugs are of favorable tolerance for patients in the treatment of OA compared with placebo. Conclusions. Lutikizumab, the new anti–Interleukin-1α/β dual variable domain immunoglobulin, showed no improvement in pain or function when compared with placebo. Selective cox-2 inhibitors and duloxetine remain the most effective and safest treatment for OA. More high-quality trials are still needed to reconfirm the findings of this study.

Background: Nerve injuries can result in detrimental functional outcomes. Currently, autologous nerve graft offers the best outcome for segmental peripheral nerve injury. Allografts are alternatives, but do not have comparable results. This study evaluated whether plasma-derived exosome can improve nerve regeneration and functional recovery when combined with decellularized nerve allografts. Methods: The effect of exosomes on Schwann cell proliferation and migration were evaluated. A rat model of sciatic nerve repair was used to evaluate the effect on nerve regeneration and functional recovery. A fibrin sealant was used as the scaffold for exosome. Eighty-four Lewis rats were divided into autograft, allograft, and allograft with exosome groups. Gene expression of nerve regeneration factors was analyzed on postoperative day 7. At 12 and 16 weeks, rats were subjected to maximum isometric tetanic force and compound muscle action potential. Nerve specimens were then analyzed by means of histology and immunohistochemistry. Results: Exosomes were readily taken up by Schwann cells that resulted in improved Schwann cell viability and migration. The treated allograft group had functional recovery (compound muscle action potential, isometric tetanic force) comparable to that of the autograft group. Similar results were observed in gene expression analysis of nerve regenerating factors. Histologic analysis showed no statistically significant differences between treated allograft and autograft groups in terms of axonal density, fascicular area, and myelin sheath thickness. Conclusions: Plasma-derived exosome treatment of decellularized nerve allograft may provide comparable clinical outcomes to that of an autograft. This can be a promising strategy in the future as an alternative for segmental peripheral nerve repair.

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