miR‐142‐5p protects against osteoarthritis through competing with lncRNA XIST

Abstract

Background The relevance between abnormal microRNA expression and osteoarthritis (OA) has been elaborated in recent studies. Hence, the present study aimed to assess the impact of miR‐142‐5p on chondrocyte growth and apoptosis. Methods To mimic OA‐like chondrocyte damage, interleukin (IL)‐1β was used for chondrocyte treatment. The expression of miR‐142‐5p, SGTB, long non‐coding RNA (lncRNA) X inactive specific transcript (XIST) and involved molecules such as Col2A1, Bcl‐2, MMP13 and Bax was determined via a quantitative reverse transcriptase‐polymerase chain reaction and western blot analyses. Functional roles of miR‐142‐5p, SGTB and XIST were monitored in 5‐ethynyl‐2'‐deoxyuridine, CCK‐8 and TUNEL experiments. Rescue analyses were conducted to consolidate the effect of the XIST/miR‐142‐5p/SGTB axis on chondrocytes in OA. Results miR‐142‐5p was down‐regulated in IL‐1β‐treated chondrocytes, whereas SGTB and XIST levels were increased. Overexpression of miR‐142‐5p stimulated proliferation and retarded apoptosis in IL‐1β‐treated chondrocytes. Meanwhile, miR‐142‐5p elevation was correlated with an elevation of Col2A1 and Bcl‐2, as well as a decline of MMP13 and Bax. A mechanistic study showed that miR‐142‐5p negatively regulated SGTB expression. Moreover, we found that lncRNA XIST could relieve the inhibition of miR‐142‐5p on SGTB expression. Augmentation of SGTB or suppression of miR‐142‐5p reversed the influence of XIST depletion on chondrocyte growth and apoptosis. Conclusions The present study has explored the fundamental role of miR‐142‐5p in IL‐1β‐treated chondrocytes, as well as the novel molecular mechanism constituted by miR‐142‐5p/SGTB/XIST in OA. Potentially, the results obtained may add new insight into OA pathogenesis.

LncRNA HOTAIR modulates chondrocyte apoptosis and inflammation in osteoarthritis via regulating miR‐1277‐5p/SGTB axis

“…Sun et al revealed that IL-1β stimulation elevated SGTB expression, and SGTB overexpression abated the inhibition of lncRNA XIST depletion on chondrocyte apoptosis by interacting with miR-142-5p. 36 Our research validated that miR-1277-5p undermined LPS-triggered chondrocyte apoptosis and inflammation through regulation of SGTB.…”

Role of lincRNA‑Cox2 targeting miR‑150 in regulating the viability of chondrocytes in osteoarthritis

“…The dysfunction of chondrocytes is responsible for OA development (18); thus, chondrocytes are commonly used to induce an ex vivo OA model through the stimulation of IL-1β. The apoptosis and proliferation of chondrocytes has also been found to be modulated by lncRNAs, such as lncRNA XIST, PVT1 and PART-1 (19)(20)(21). The present study investigated the effect of lincRNA-Cox2 on the proliferation and apoptosis of chondrocytes, demonstrating an important role for lincRNA-Cox2 in the development of OA.…”

“…However, despite the diverse aetiologies and pathogenesis of OA, a detailed pathogenic mechanism has not yet been elucidated. Recent focus on the epigenetic-regulating mechanisms of OA has revealed that numerous lncRNAs serve important functions in the development of inflammatory diseases including OA, such as lncRNAs XIST and PVT1 (19,20). lincRNA-Cox2, a class of lncRNAs localised to both the cytosolic and nuclear compartments, affects the expression of hundreds of inflammatory genes (such as Tlr1, Il6 and Il23a) and regulates the inflammatory response (12).…”

LincRNA-Cox2 targeting miR-150 regulating the proliferation and apoptosis of chondrocytes in osteoarthritis

“…4C and D). [19,14]. LincRNA-Cox2, a class of lncRNA localized to both thecytosolic and nuclear compartments, has ability to affect the expression of hundreds of inflammatory genes and regulate inflammatory response [2].…”

“…Therefore, their dysfunction is responsible for OA development [17]. The apoptosis and growth of chondrocytes were also found to be modulated by lncRNA, such as lncRNA XIST, PVT1 and PART-1 [19,14,13]. In this study, we investigated the effect of LincRNA-Cox2 on the proliferation and apoptosis of chondrocytes supporting an important role for LincRNA-Cox2 in the development of OA.…”