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Objectives: Circular RNAs (circRNA) expression aberration has been identified in various human diseases. In this study, we investigated whether circRNAs could act as competing endogenous RNAs to regulate the pathological process of osteoarthritis (OA).Methods: CircRNA deep sequencing was performed to the expression of circRNAs between OA and control cartilage tissues. The regulatory and functional role of CircSERPINE2 upregulation was examined in OA and was validated in vitro and in vivo, downstream target of CircSERPINE2 was explored. RNA pull down, a luciferase reporter assay, biotin-coupled microRNA capture and fluorescence in situ hybridisation were used to evaluate the interaction between CircSERPINE2 and miR-1271-5 p, as well as the target mRNA, E26 transformation-specific-related gene (ERG). The role and mechanism of CircSERPINE2 in OA was also explored in rabbit models.Results: The decreased expression of CircSERPINE2 in the OA cartilage tissues was directly associated with excessive apoptosis and imbalance between anabolic and catabolic factors of extracellular matrix (ECM). Mechanistically, CircSERPINE2 acted as a sponge of miR-1271-5 p and functioned in human chondrocytes (HCs) through targeting miR-1271-5 p and ERG. Intra-articular injection of adeno-associated virus-CircSERPINE2-wt alleviated OA in the rabbit model.Conclusions: Our results reveal an important role for a novel circRNA-CircSERPINE2 in OA progression. CircSERPINE2 overexpression could alleviate HCs apoptosis and promote anabolism of ECM through miR-1271-ERG pathway. It provides a potentially effective therapeutic strategy for OA progression. [ABSTRACT FROM AUTHOR]

Background: Orthopaedic surgeons must play an important role in the secondary prevention of fragility fractures; however, some surgeons are more aware than others of their responsibility regarding fracture prevention. The purpose of the present study was to identify which factors can lead to a higher sensitivity for fracture prevention.Methods: A cross-sectional survey was distributed to orthopaedic surgeons via online invitation or at academic conferences in China from July through October 2015. A total of 452 surgeons responded. As the primary outcome measure, we created a sensitivity scoring system for fracture prevention based on the respondents' answers to 5 questions regarding behavior in the following areas: risk-factor evaluation, pharmacologic therapy, nonpharmacologic therapy, patient education, and follow-up. Multivariable linear regression and multivariable logistic regression analyses were used to identify factors related to surgeon sensitivity to fracture prevention.Results: Very few surgeons reported having received adequate training regarding fracture prevention or reading guidelines or other fracture prevention literature (22% and 30%, respectively). Most respondents initiated pharmacologic or nonpharmacologic therapy (82% and 75%, respectively) for the treatment of confirmed osteoporosis among patients with fragility fractures, but only half performed a risk-factor evaluation, patient education, or timely patient follow-up (51%, 52%, and 48%, respectively). In the multivariable linear regression model, the orthopaedic surgeon's age (β = 0.09, p = 0.003), self-rated knowledge level regarding osteoporosis or related issues (β = 0.16, p < 0.001), self-perceived effectiveness in using preventive measures for patients with a fragility fracture (β = 0.62, p < 0.001), and use of clinical pathways for fragility fractures in his or her workplace (β = 1.24, p < 0.001) were independently associated with sensitivity scores for fracture prevention. Similar results were obtained from a multivariable logistic regression model.Conclusions: In China, the sensitivity of orthopaedic surgeons to the secondary prevention of fragility fractures is relatively low. Implementation of a comprehensive prevention approach and targeted continuing medical education are required to encourage surgeons to take greater responsibility for screening, treating, educating, and following their patients with fragility fractures. [ABSTRACT FROM AUTHOR]

Background: Acupuncture reportedly relieves chronic knee pain and improves physical function in patients diagnosed with osteoarthritis, but the duration of these effects is controversial. The aim of this study was to evaluate the temporal effects of acupuncture on chronic knee pain due to knee osteoarthritis by means of a meta-analysis.Methods: The PubMed, Embase, and Cochrane Central Register of Controlled Trials databases were searched for studies published through March 2015. Ten randomized controlled trials of acupuncture compared with sham acupuncture, usual care, or no intervention for chronic knee pain in patients with clinically diagnosed or radiographically confirmed knee osteoarthritis were included. All of the studies were available in English. Weighted mean differences (WMDs), 95% confidence intervals (CIs), publication bias, and heterogeneity were calculated.Results: The acupuncture groups showed superior pain improvement (p < 0.001; WMD = -1.24 [95% CI, -1.92 to -0.56]; I(2) > 50%) and physical function (p < 0.001; WMD = 4.61 [95% CI, 2.24 to 6.97]; I(2) > 50%) in the short term (up to 13 weeks). The acupuncture groups showed superior physical function (p = 0.016; WMD = 2.73 [95% CI, 0.51 to 4.94]; I(2) > 50%) but not superior pain improvement (p = 0.199; WMD = -0.55 [95% CI, -1.39 to 0.29]; I(2) > 50%) in the long term (up to 26 weeks). Subgroup analysis revealed that the acupuncture groups tended to have better outcomes compared with the controls. Significant publication bias was not detected (p > 0.05), but the heterogeneity of the studies was substantial.Conclusions: This meta-analysis demonstrates that acupuncture can improve short and long-term physical function, but it appears to provide only short-term pain relief in patients with chronic knee pain due to osteoarthritis.Level Of Evidence: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence. [ABSTRACT FROM AUTHOR]

Hypoxia is an indispensable factor for cancer progression and is closely associated with the Warburg effect. Circular RNAs (CircRNA) have garnered considerable attention in molecular malignancy therapy as they are potentially important modulators. However, the roles of circRNAs and hypoxia in osteosarcoma (OS) progression have not yet been elucidated. This study reveals the hypoxia-sensitive circRNA, Hsa&#95;circ&#95;0000566, that plays a crucial role in OS progression and energy metabolism under hypoxic stress. Hsa&#95;circ&#95;0000566 is regulated by hypoxia-inducible factor-1α (HIF-1α) and directly binds to it as well as to the Von Hippel-Lindau (VHL) E3 ubiquitin ligase protein. Consequentially, binding between VHL and HIF-1α is impeded. Furthermore, Hsa&#95;circ&#95;0000566 contributes to OS progression by binding to HIF-1α (while competing with VHL) and by confers protection against HIF-1α against VHL-mediated ubiquitin degradation. These findings demonstrate the existence of a positive feedback loop formed by HIF-1α and Hsa&#95;circ&#95;0000566 and the key role they play in OS glycolysis. Taken together, these data indicate the significance of Hsa&#95;circ&#95;0000566 in the Warburg effect and suggest that Hsa&#95;circ&#95;0000566 could be a potential therapeutic target to combat OS progression., Competing Interests: Conflict of Interest The authors declare that there are no competing financial interests related to this study., (copyright: © 2022 Shen et al.)

Osteoarthritis (OA) is a very common chronic joint dysfunction, and there is currently a poor understanding of its etiology and pathogenesis. Therefore, there are no active disease-modifying drugs currently available for clinical treatment. Several natural compounds have been shown to play a role in inhibiting OA progression. The present study is aimed at investigating the curative effects of acacetin, a natural flavonoid compound, against OA. Our results demonstrated that MMP-1, MMP-3, and MMP-13 were highly expressed in OA specimens. Acacetin inhibited the interleukin-1 β - (IL-1 β -) induced expression of MMP-1, MMP-3, and MMP-13in chondrocytes by blocking nuclear factor- κ B (NF- κ B) signaling pathways. Furthermore, we found that acacetin suppressed OA progression and inhibited the expression of MMP-1, MMP-3, and MMP-13 in ACLT-induced OA mice. Taken together, our study revealed that acacetin may serve as a potential drug for treating OA., Competing Interests: The authors have declared no conflicts of interest., (Copyright © 2020 Jian Chen et al.)

Purpose: Prevailing evidences have demonstrated that circular RNAs (circRNAs) are closely associated with various stages of carcinogenesis. However, very few studies have delineated the specific mechanism of association between circRNAs and osteosarcoma (OS). It offers a novel insight that circRNAs can be explored as a potential therapeutic strategy for OS., Materials and Methods: In this study, circTUBGCP3 was chosen from the existing reported circRNA microarray data obtained from OS cell lines and normal bone cells. Subsequently, qRT-PCR was performed to evaluate the expression level of circTUBGCP3 in OS samples and cell lines. Functional assays were conducted to estimate the impact of circTUBGCP3 on human OS cells proliferation, vitality, survivability, and migration. Western blot, luciferase reporter and in vivo tumorigenesis assays were performed to analyze the signaling pathways underlying the interaction of circTUBGCP3, miR-30b, and Vimentin., Results: The data indicate that circTUBGCP3 may act as a sponge of miR-30b that further alters the expression of Vimentin, and promotes the proliferation and metastatic properties of OS cells., Conclusion: circTUBGCP3 serves as a tumor promoter in tumorigenesis by increasing the possibilities of OS initiation and proliferation., Competing Interests: The authors report no conflicts of interest in this work., (© 2020 Xu et al.)

Objectives: In traditional Chinese medicine, gamboge can detoxify bodies, kill parasites, and act as a hemostatic agent. Recent studies have demonstrated that gambogic acid (GBA) suppressed inflammation in arthritis, and also presented antitumor effect. Thus, this study investigated the new biological properties of GBA on macrophages., Materials and Methods: RAW 264.7 cells were pretreated with GBA at different concentrations (10, 20, 40, 80, 160, 320 nM) for 24 hrs, and then cell viability was measured using Cell Counting Kit (CCK)-8 assays. Pro-inflammatory cytokines such as TNF-α, IL-6 and IL-1β were determined using ELISA kits and qPCR. Then nitrite concentration was calculated according to a standard curve. At last, the effect of GBA on MAPK and NF-κB signaling pathways was assessed by western blot and luciferase reporter gene assay., Results: GBA (IC50: 260 nM) suppressed the TNF-α, IL-6 and IL-1β expression induced by lipopolysaccharide (LPS) in RAW 264.7 cells. The expression of TNF-α, IL-6 and IL-1β decreased to 30-50% and 70-75% in the high-dose (160 nM) and low-dose (40 and 80 nM) GBA groups, respectively. Furthermore, the nitric oxide (NO) production and the activation of NF-κB, ERK, and JNK pathways were significantly reduced in high-dose (160 nM) GBA only, while p38 pathway was inhibited at both low (40 and 80 nM) and high (160 nM) concentration of GBA., Conclusion: These data suggested that GBA inhibited LPS-induced production of pro-inflammatory cytokines including TNF-α, IL-6 and IL-1β mainly through the suppression of the p38 pathway.