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Cartilage
12, 2021;13 (2_suppl): 1412S-1420S.

FGD5-AS1 Inhibits Osteoarthritis Development by Modulating miR-302d-3p/TGFBR2 Axis.

Yue Yang, Zhibo Sun, Feng Liu, Yuanzhang Bai, Fei Wu
Author Information
  1. Yue Yang: Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China. ORCID
  2. Zhibo Sun: Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China.
  3. Feng Liu: Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China.
  4. Yuanzhang Bai: Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China.
  5. Fei Wu: Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China.
PMID: 33834880 DOI: 10.1177/19476035211003324

Abstract

OBJECTIVE: Osteoarthritis (OA) is a common joint disorder, accompanied by extracellular matrix (ECM) degradation. Reportedly, long noncoding RNAs (lncRNAs) are involved in OA pathogenesis. However, the role of lncRNA FYVE, RhoGEF, and PH domain containing 5 antisense RNA 1 (FGD5-AS1) in OA development is still not fully clarified. This study was aimed to clarify the role of FGD5-AS1 in OA.
METHODS: FGD5-AS1 and miR-302d-3p expression levels were determined in cartilage tissues and chondrocytes by quantitative real-time polymerase chain reaction (qRT-PCR). Chondrocytes (C20/A4 cells) were stimulated with interleukin 1β (IL-1β) to mimic the inflammatory environment of OA. Cell viability was detected by cell counting kit-8 and 5-ethynyl-2'-deoxyuridine assays. Cell apoptosis was measured by the caspase-3 activity assay and flow cytometry. Transforming growth factor beta receptors II (TGFBR2), matrix metalloproteinase 13 (MMP-13), and ADAM metallopeptidase with thrombospondin type 1 motif 5 expression levels were examined by qRT-PCR or Western blot. The regulatory relationships among FGD5-AS1, miR-302d-3p, and TGFBR2 were predicted by the StarBase v2.0, miRanda, miRDB, and TargetScan databases, and confirmed by dual-luciferase reporter assay and RNA immunoprecipitation assay.
RESULTS: FGD5-AS1 and TGFBR2 expression levels were downregulated while miR-302d-3p expression was increased in cartilage tissues of OA patients. Knocking down FGD5-AS1 inhibited the viability of C20/A4 cells but induced apoptosis and ECM degradation, while FGD5-AS1 overexpression exerted opposite effects. MiR-302d-3p was identified as a target of FGD5-AS1, and TGFBR2 was identified as a target of miR-302d-3p. FGD5-AS1 positively regulated TGFBR2 expression by repressing miR-302d-3p expression, and miR-302d-3p inhibition or TGFBR2 restoration reversed the changes of cell viability, apoptosis, and ECM degradation induced by FGD5-AS1 knockdown.
CONCLUSION: FGD5-AS1 can probably inhibit OA progression by regulating miR-302d-3p/TGFBR2 axis.

Keywords

FGD5-AS1 MiR-302d-3p TGFBR2 osteoarthritis

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MeSH Term

Cell Proliferation
Guanine Nucleotide Exchange Factors
Humans
MicroRNAs
Osteoarthritis
RNA, Long Noncoding
Receptor, Transforming Growth Factor-beta Type II
Signal Transduction

Chemicals

FGD5 protein, human
Guanine Nucleotide Exchange Factors
MicroRNAs
RNA, Long Noncoding
Receptor, Transforming Growth Factor-beta Type II
TGFBR2 protein, human
Journal Article

Word Cloud

Created with Highcharts 10.0.0FGD5-AS1OATGFBR2miR-302d-3pexpressionECMdegradationlevelsviabilityapoptosisassayOsteoarthritismatrixrole5RNA1cartilagetissuesqRT-PCRC20/A4cellsCellcellinducedMiR-302d-3pidentifiedtargetmiR-302d-3p/TGFBR2OBJECTIVE:commonjointdisorderaccompaniedextracellularReportedlylongnoncodingRNAslncRNAsinvolvedpathogenesisHoweverlncRNAFYVERhoGEFPHdomaincontainingantisensedevelopmentstillfullyclarifiedstudyaimedclarifyMETHODS:determinedchondrocytesquantitativereal-timepolymerasechainreactionChondrocytesstimulatedinterleukin1βIL-1βmimicinflammatoryenvironmentdetectedcountingkit-85-ethynyl-2'-deoxyuridineassaysmeasuredcaspase-3activityflowcytometryTransforminggrowthfactorbetareceptorsIImetalloproteinase13MMP-13ADAMmetallopeptidasethrombospondintypemotifexaminedWesternblotregulatoryrelationshipsamongpredictedStarBasev20miRandamiRDBTargetScandatabasesconfirmeddual-luciferasereporterimmunoprecipitationRESULTS:downregulatedincreasedpatientsKnockinginhibitedoverexpressionexertedoppositeeffectspositivelyregulatedrepressinginhibitionrestorationreversedchangesknockdownCONCLUSION:canprobablyinhibitprogressionregulatingaxisInhibitsDevelopmentModulatingAxisosteoarthritis

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