RNA sequencing reveals the circular RNA expression profiles of the infrapatellar fat pad/synovium unit

Abstract

Background: The infrapatellar fat pad (IPFP) and synovium are reported to act as a functional unit, with emerging roles in the pathophysiology of knee osteoarthritis (KOA). Circular RNAs (circRNAs) are involved in the pathogenesis of KOA, especially in cartilage homeostasis regulation. Nevertheless, the regulatory mechanisms of circRNAs in the KOA IPFP/synovium unit remain to be elucidated. Therefore, the current study aimed to investigate alterations in the expression of circRNAs and predict their functions in the KOA IPFP/synovium unit using bioinformatics analysis.Methods: In brief, 6 synovium and IPFP specimens were collected, in which 3 from patients with KOA and 3 from controls. Then, circRNA sequencing was conducted on 2 KOA synovium and IPFP specimens as well as 1 control to investigate the expression profiles of circRNAs. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Reactome signaling pathway analyses were employed to predict the functions of the differentially expressed circRNAs. Based on the miRNA sponge theory, we constructed a circRNA-miRNA network to predict the molecular regulatory mechanism of these circRNAs. Venn analysis was performed to confirm the circRNAs and miRNAs expressed in both synovium and IPFP. Realtime quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was also used to validate the expression levels of circRNAs that were co-expressed in both synovium and IPFP.Results: A total of 65 and 72 circRNAs were differentially expressed in KOA synovium and IPFP, respectively (fold change ≥2, P<0.05). After obtaining the parental genes of differentially expressed circRNAs, the top 10 enrichment GO entries, KEGG pathways, and Reactome pathways were annotated. Furthermore, hsa_circ_0005265 was found to be down-regulated in both synovium and IPFP, which was validated by qRT-PCR. The circRNA-miRNA network was created to annotate the probable regulatory mechanisms of the differentially expressed circRNAs, which consequently confirmed 2 target miRNAs (hsa-miR-6769b-5p and hsa-miR-1249-5p) associated with hsa_circ_0005265 in both synovium and IPFP.Conclusions: Our outcomes bring us closer to understanding the potential mechanism of the IPFP/ synovium unit in the progression of KOA and finding new molecular targets for KOA therapy.

Transcriptomes of human primary skin fibroblasts of healthy individuals reveal age‐associated mRNAs and long noncoding RNAs

“…While the roles of the vast majority of circRNAs are poorly understood, a few of the validated circRNAs in our study were previously associated with age‐related declines or disease. For example, hsa_circ_0000591 and hsa_circ_0071106 were previously linked to knee osteoarthritis and type 2 diabetes, respectively (Jiang et al, 2021; Yingying et al, 2021), whereas delivery of hsa_circ_0001610 via EVs from tumor‐associated macrophages reduced radiosensitivity in endometrial cancer (Gu et al, 2021). Notably, we identified the RBP interleukin enhancer‐binding factor 3 (ILF3) as interacting with linear lncRNAs that changed with age (Figure 4b), and ILF3 coordinates the biogenesis of some circRNAs during viral infection (Li et al, 2017).…”

CircRNAs in osteoarthritis: research status and prospect

“…On the other hand, the infrapatellar fat pad and the surrounding synovium are also essential tissues involved in regulating the intra-articular environment. Circular RNA expression profiles of the infrapatellar fat pad/synovium unit reveal that hsa_circ_0005265 was down-expressed in both OA synovium and IPFP, targeting hsa-miR-6769b-5p and hsa-miR-1249-5p ( Jiang et al, 2021a ). However, the molecular mechanisms of differentially expressed circRNAs in OA synovium or infrapatellar fat pad in the progression of OA have not been thoroughly investigate.…”