CircFADS2 is downregulated in osteoarthritis and suppresses LPS-induced apoptosis of chondrocytes by regulating miR-195-5p methylation
Graphical Abstract
Introduction
As the most common type of arthritis, osteoarthritis (OA) is a joint disease caused by the breakdown of joint tissues over time (Glyn-Jones et al., 2015, Zhang and Jordan, 2010). OA mainly affects elderly people. It has been estimated that more than 13% of females and 10% of males older than 60 years old are suffering from OA (Collins et al., 2018, Rahmati et al., 2017, Loeser, 2017). Osteoarthritis is one of the most common causes of chronic pain, disability, as well as socioeconomic cost worldwide (Collins et al., 2018, Rahmati et al., 2017, Loeser, 2017). However, current treatment approaches for OA can only control disease conditions and relieve symptoms, such as chronic pain, and no cure is available yet (Sinusas, 2012). Therefore, more effective therapies are still needed for the treatment of OA.
Besides aging, studies have revealed a considerable number of molecular players with critical functions in the pathogenesis of OA (Lee et al., 2013, Wang et al., 2011, Xia et al., 2014). For instance, the chronic innate inflammatory pathways have been demonstrated to be potential therapeutic targets for the treatment of OA (Conaghan et al., 2019, Herrero-Beaumont et al., 2019). However, molecular targeted therapies for OA are still under research. Therefore, identification of targets is needed to screen for the ones with high safety and efficacy.
As covalently closed single strand RNAs, circular RNAs (circRNAs), or self-closed long non-coding RNAs, have limited protein-coding capacity, but can regulate gene expression at different levels to participate in human diseases including OA (Wu et al., 2019, Ehrlich, 2019). Certain circRNAs have been characterized as potential diagnostic biomarkers and therapeutic targets for OA (Wu et al., 2019, Ehrlich, 2019). However, the functions of most circRNAs in OA are unknown, which limits the development of circRNAs as potential targets to treat OA. It has been reported that circRNA circFADS2 protects cells from LPS (Lipopolysaccharide)-induced cell injury, which contributes to OA (Li et al., 2019). Our preliminary sequencing analysis data revealed the closely correlation between circFADS2 and miR-195-5p (data not shown), which is a critical player in OA (Shu et al., 2019). This study was therefore carried out to study the role of circFADS2 in OA, with a focus on its interactions with miR-195-5p.
Section snippets
Research subjects
This study included 63 OA patients (42 females and 21 males, mean age 59.1 +/- 5.8 years old) and 63 healthy controls (42 females and 21 males, mean age 59.1+/-5.8 years) who were admitted to the Affiliated Hospital of Southwest Medical University between March 2019 and August 2020. This study was approved by the Ethics Committee of this hospital. All procedures performed in studies involving human participants were in accordance with the 1964 Helsinki declaration. All OA patients were
Altered expression of circFADS2 and miR-195-5p in OA patients
The expression levels of circFADS2 and miR-195-5p in synovial fluid samples from the 63 OA patients and 63 healthy controls were detected by RT-qPCRs. Compared to the control group, the expression levels of circFADS2 were significantly lower (Fig. 1A, p < 0.001), and the expression levels of miR-195-5p were significantly higher (Fig. 1B, p < 0.001) in the OA group. Therefore, altered expression of circFADS2 and miR-195-5p might participate in OA.
CircFADS2 was inversely correlated with miR-195-5p
Correlations between circFADS2 and miR-195-5p
Discussion
In this study we explored the role of circFADS2 in OA and investigated its interaction with miR-195-5p, which is a critical player in OA (Shu et al., 2019). We found that circFADS2 was downregulated in OA and it downregulated miR-195-5p through methylation to suppress the apoptosis of chondrocytes induced by LPS.
CircFADS2 has been characterized as an oncogene in lung cancer and colorectal cancer (Zhao et al., 2018, Xiao et al., 2020). CircFADS2 is upregulated in cancers, and it not only
Conclusions
In conclusion, circFADS2 is downregulated in OA and it may downregulate miR-195-5p through methylation to suppress the apoptosis of OA-derived chondrocytes induced by LPS.
Ethics approval
This study was approved by the ethics committee of The Affiliated Hospital of Southwest Medical University. All procedures performed in studies involving human participants were in accordance with the 1964 Helsinki declaration. Written informed consent was obtained from all individual participants included in the study.
Consent for publication
Not applicable.
Availability of data and material
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
Funding
No funding received.
Authors' contributions
HWZ: study concepts, literature research, experimental studies, manuscript writing; XBL: study concepts, study design, literature research, manuscript preparation and editing; JHG: data acquisition, statistical analysis and manuscript preparation. All authors read and approved the final manuscript.
Declaration of Competing Interest
The authors declare that they have no competing interests.
Acknowledgements
Not applicable.
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