Up-regulation of long non-coding RNA CYTOR induced by icariin promotes the viability and inhibits the apoptosis of chondrocytes

Abstract

Background Icariin (ICAR) is the main effective component extracted from epimedium, and is reported to have the potential to treat osteoarthritis (OA). However, its pharmacological function on chondrocytes has not been fully clarified. Methods Different doses of ICAR were used to treat chondrocyte cell lines, including CHON-001 and ATDC5. Then the expressions of different lncRNAs were measured by qRT-PCR. Interleukin-1β (IL-1β) was used to simulate the inflammatory response environment of chondrocytes. Overexpression plasmids and short hairpin RNAs of lncRNA CYTOR were used to construct gain-of-function and loss of function models. CCK-8 was conducted to determine the cell viability. Flow cytometry was used to detect the apoptosis of chondrocytes. Enzyme-linked immunosorbent assay (ELISA) was adopted to measure the contents of inflammatory factors (IL-6, IL-8, TNF-α) in the supernatant of the chondrocytes. Results Compared with other lncRNAs, CYTOR was changed most significantly in both CHON-001 and ATDC5 cells after treatment with ICAR. ICAR promotes the viability and inhibits the apoptosis of CHON-001 and ATDC5 cells induced by IL-1β, accompanied with reduced levels of inflammatory factors. Overexpression of CYTOR facilitated the viability of chondrocytes, while repressed their apoptosis and inflammatory response. What’s more, knockdown of CYTOR reversed the protective effects of ICAR on chondrocytes. Conclusion CYTOR was a pivotal lncRNA involved in the protective function of ICAR on chondrocytes.

Osteoarthritis in the Elderly Population: Preclinical Evidence of Nutrigenomic Activities of Flavonoids

“…Flavonols are interesting for their biological activity, such as being antioxidant, antimicrobial, hepatoprotective, and anti-inflammatory, and, more recently, they have also been studied as potential anticancer agents. In our research, we found twelve manuscripts on six molecules: astilbin, galangin (3,5,7-trihydroxyflavone, Gal), hyperoside, icariin, quercetin (Que), and rutin [ 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 ]. Astilbin is a flavonol identified in Dimorphandra mollis , Hypericum perforatum, and other natural plants, and it is also extracted from grapes.…”

“…ICA inhibits IL-1β-induced phosphorylation of PI3K, AKT, and mTOR, and attenuates the excessive production of MMP-3 and promotes the production of Col-II. Silencing ULK1 reverses the protective effect of ICA in OA chondrocytes, demonstrating that ULK1 and the autophagy process are essential for ICA’s mechanism of action [ 70 ]. In Wang et al (2021), ICA induced the expression of an lncRNA, Cytoskeleton Regulator RNA (CYTOR), implicated in age-related articular cartilage degradation.…”

New Insights into the Roles of lncRNAs as Modulators of Cytoskeleton Architecture and Their Implications in Cellular Homeostasis and in Tumorigenesis

“…Curiously, the upregulated expression of CYTOR has been reported not only in vitro models but also in patients with several breast cancer classes such as HER2 or triple negative carcinomas subtypes [64]. Moreover, emerging evidence has pointed out that CYTOR is not a breast cancer specific lncRNA, showing upregulated expression in several other types of cancer such as nasopharyngeal, gastric, colon, or hepatocellular carcinoma and also correlating with poor prognoses and increased aggressiveness [30,31,[65][66][67][68]. Cytoskeletal dynamics require the participation of several modulating factors which regulate G-actin assembly and de-assembly to form filaments.…”

Development of Nanomaterials to Target Articular Cartilage for Osteoarthritis Therapy

“…Long non-coding RNA (lncRNA) induced by icariin is also confirmed to promote proliferation and repress the loss of chondrocytes in an inflammatory microenvironment. Cytoskeleton regulator RNA (CYTOR) is a kind of lncRNA, Wang, G. et al ( Wang et al, 2021 ) demonstrated that the CYTOR knockdown could reverse the anti-OA drug’s protective effect in chondrocytes, indicating CYTOR to be a promising chondrocyte-targeted nanodrug for OA.…”