Circular RNA circ_0114876 regulates osteoarthritis through upregulating ADAM10 via targeting miR-1227-3p.

BACKGROUND: Osteoarthritis (OA) was a chronic degenerative joint disease. The dysregulation of circular RNAs (circRNAs) has been identified in OA progression. However, the function and regulation mechanism of circ_0114876 in OA remains largely unknown. METHOD: Firstly, we used LPS-treated C28/I2 cells as a cellular model of OA. Quantificational real-time polymerase chain reaction (qRT-PCR) was used to determine the expression levels of circ_0114876, miRNA-1227-3p, and ADAM10 in OA chondrocytes. Cell Counting Kit-8 (CCK8), 5-ethynyl-20-deoxyuridine (EdU) incorporation assays, flow cytometry, Enzyme-linked immunosorbent assay (ELISA) kit, and western blot were applied to confirm cell proliferation, apoptosis, inflammation, and extracellular matrix. of circ_0114876 in vitro. The interaction between circ_0114876 and its downstream target (miR-1227-3p) and mRNA target ADAM metallopeptidase domain 10 (ADAM10), was evaluated by luciferase assay and RNA immunoprecipitation (RIP) assay. RESULT: Circ_0114876 and ADAM10 were upregulated and miR-1227-3p was decreased in OA tissues and LPS-treated chondrocytes. Low expression of circ_0114876 promoted proliferation and inhibited apoptosis, inflammation, and extracellular matrix of the LPS-treated chondrocytes. Mechanistically, circ_0114876 functioned in human chondrocytes through targeting miR-1227-3p and ADAM10. Furthermore, miRNA-1227-3p inhibitor reversed the effect of circ_0114876 knockdown on the OA chondrocytes, and ADAM10 overexpression reversed the effect of miR-1227-3p mimic on the OA chondrocytes. CONCLUSION: Circ_0114876 was increased in OA tissues and cells. Circ_0114876 facilitated the progression in the LPS-induced OA cell model via regulating the miR-1227-3p/ADAM10 axis. This study would provide a potentially effective therapeutic strategy for OA progression.

Evidence of Chinese herbal fumigation for knee osteoarthritis: A protocol for systematic review and meta-analysis.

BACKGROUND: Knee osteoarthritis (KOA) is the most common cause of musculoskeletal pain and disability worldwide. Chinese herbal fumigation, an external therapy, is commonly used for the treatment of KOA, while there is no systematic review or meta-analysis designed to evaluate the effects of Chinese herbal fumigation on KOA. METHODS: Seven databases including Cochrane Central Register of Controlled Trials, EMBASE, PubMed, China National Knowledge Infrastructure, Wanfang data, VIP, and Chinese Biomedical Literature Database will be searched up to October 31, 2020. Data that meet the inclusion criteria will be extracted and analyzed by using RevMan V.5.3 software. Two reviewers will assess quality of the included studies based on the Cochrane Collaboration risk of bias tool. The funnel plot and Begg test will be used to evaluate publication bias. And Grading of Recommendations Assessment, Development and Evaluation will be employed to assess the quality of evidence. RESULTS: This study will provide high-quality evidence for Chinese herbal fumigation for the treatment of KOA in terms of effectiveness and safety. CONCLUSION: This systematic review will provide evidence to help us confirm the clinical efficacy of Chinese herbal fumigation in the treatment of KOA.

Electroacupuncture for the Prevention of Postoperative Cognitive Dysfunction Among Older Adults Undergoing Hip and Knee Arthroplasty: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background: Postoperative cognitive dysfunction (POCD) is a common surgical complication in elderly patients undergoing hip and knee replacement. Electroacupuncture (EA) may have a protective effect on postoperative cognitive function, but relevant evidence remains uncertain. Objective: To systematically evaluate the evidence of EA for the prevention of POCD after total joint arthroplasty. Methods: PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), China National Knowledge Infrastructure (CNKI), Wanfang Data, VIP, and Chinese Biomedical Literature Database (CBM) databases were searched until May 1, 2021. Randomized controlled trials (RCTs) in which patients undergoing hip and knee replacement pretreated with EA for preventing POCD were included. The risk of bias was assessed by the Cochrane Collaboration tool. Meta-analysis was performed using Review Manager version 5.4. Results: A total of 11 RCTs with 949 patients were identified. Meta-analysis showed that compared with controls, EA pretreatment significantly reduced the incidence of POCD at 1, 3, and 7 days and 3 and 6 months after the operation. EA was also superior in improving the Mini-Mental State Examination (MMSE) scores on the third postoperative day, but not on the first postoperative day. Neuron-specific enolase (NSE) and interleukin-1ß (IL-1ß) in the EA group were significantly lower than that in the control group. There was no difference in S100ß between the EA group and the control group. Compared to the control group, tumor necrosis factor-α (TNF-α) levels were not significantly lower in the EA group at postoperative hour 0, while significantly decreased at postoperative hours 24 and 48. Conclusion: Our results suggest that EA pretreatment is an effective adjunctive therapy for reducing the incidence of POCD for patients receiving total joint replacement surgery. Its effect was embodied in improving the MMSE scores and NSE, IL-1ß, and TNF-α levels, whereas it had no significant effect on S100ß levels. Meanwhile, the benefits of EA for improving POCD need further strengthening and support from more large-scale, high-quality, and good-homogeneity RCTs. Systematic Review Registration: https://osf.io/xb3e8.