Long non-coding RNA ZNFX1 antisense 1 (ZFAS1) suppresses anti-oxidative stress in chondrocytes during osteoarthritis by sponging microRNA-1323

Abstract

LncRNAs play a regulatory role in osteoarthritis (OA); however, the detailed mechanism remains to be elucidated. This study aimed to investigate the role of lncRNA zinc finger NFX1-type containing 1 (ZNFX1) antisense 1 (ZFAS1) in OA progression and explore its possible mechanismsagainst oxidative stress. Human cartilage specimens were obtained from 10 patients without OA who underwent traumatic amputation and 25 patients with OA who underwent total knee replacement surgery. Chondrocytes were prepared from harvested articular cartilage. ZFAS1, nuclear factor erythroid 2-related factor 2 (Nrf2), and heme oxygenase 1 (HO-1) expression levels were analyzed using quantitative reverse transcription PCR and WB. The chondrocyte growth was indicated by MTT and colony formation assays. Chondrocyte apoptosis, reactive oxygen species generation, and anti-oxidative enzymes activities were also measured. ZFAS1 expression was reduced in OA samples and lipopolysaccharide (LPS)-treated chondrocytes used as an OA cell model mimic. ZFAS1 overexpression facilitated proliferation and repressed oxidative stress, inflammation, and apoptosis in LPS-induced chondrocytes. ZFAS1 also activated the anti-oxidative Nrf2-HO-1 pathway. ZFAS1 directly targeted miR-1323, which partially reversed the effects of ZFAS1 on chondrocyte proliferation, oxidative stress, inflammation, and apoptosis. Furthermore, Nrf2 was negatively regulated by miR-1323. The effect of miR-1323 inhibition was partly abrogated by the administration of brusatol, an Nrf2 inhibitor. Collectively, the results showed that ZFAS1 promoted chondrocyte proliferation and repressed oxidative stress, possibly by regulating the novel miR-1323-Nrf2 axis of the inflammation and apoptosis triggered by LPS, indicating that ZFAS1 is a promising therapeutic target for OA.

LncRNA-mediated cartilage homeostasis in osteoarthritis: a narrative review

“…Brusatol is a drug that inhibits Nrf2-mediated glucose metabolism ( 112 ). Gu’s team found that brusatol could partially abrogate the inhibitory effect of MiR-1323 on IncRNA ZFAS1 to promote chondrocyte proliferation and inhibit oxidative stress ( 113 ). This finding suggested that this compound may be a candidate drug for OA patients with reduced levels of IncRNA ZFAS1 expression.…”

LncRNA ZFAS1 Alleviated NLRP3 Inflammasome-Mediated Pyroptosis through Regulating miR-96-5p/Smad7 Signaling in Allergic Rhinitis

“…But, a previous study indicated that ZFAS1 sponged miR-34b-5p to elevate the expression of sirtuin 1 (SIRT1), which alleviated inflammatory response in sepsis-induced myocardial injury [9]. Moreover, it was reported that ZFAS1 directly targeted miR-1323, which further repressed oxidative stress and inflammation in osteoarthritis [10]. These studies suggested its protective ability in inflammatory response.…”

The emerging role of lncRNAs in osteoarthritis development and potential therapy

“…LncRNA ZNFX1 antisense 1 (ZFAS1) reduced anti-oxidative stress via sponge of miR-1323 in osteoarthritis ( Gu et al, 2022 ). LncRNA PILA enhanced the activity of PRMT1 and activated NF-κB pathway in osteoarthritis ( Tang et al, 2022 ).…”