lncRNA HAND2-AS1 is Down Regulated in Osteoarthritis and Regulates IL‐6 Expression in Chondrocyte

Abstract

Background: Osteoarthritis (OA) is a leading cause of disability. The incidence of OA is progressively rising due to the diminishing levels of physical activity and ever-expanding ageing population. However, the mainstay for OA treatment only can improve symptoms without delay the progression of this severe disease. This study aimed to explore the biological role and clinical function of lncRNA HAND2-AS1 in OA.

Methods: Blood samples and synovial fluid were collected from OA patients and normal subjects. HAND2-AS1 expression was detected by qRT-PCR and IL-6 expression was detected by ELISA; The plasma levels of HAND2-AS1 were also detected in different ages, stages and gender of OA patients and controls. Furthermore, the ROC curve was used to analyze whether HAND2-AS1 can distinguish OA patients from normal subjects. Also, Pearson correlation coefficient analysis was used to analyze the correlation between lncRNA HAND2-AS1 and IL-6. In addition, western blot was used to detect the IL-6 level upon HAND2-AS1 overexpression in chondrocytes and qRT-PCR was used to detect the HAND2-AS1 level after endogenous IL-6 treatment.

Results: HAND2-AS1 and IL-6 were dysregulated in plasma and synovial fluid of OA patients. The expression of HAND2-AS1 in plasma of OA patients was decreased with aging and progression. Furthermore, HAND2-AS1 downregulation effectively distinguished OA patients from the healthy controls. Overexpression of HAND2-AS1 inhibited IL‐6 expression in chondrocytes, while treatment with exogenous IL‐6 did not affect HAND2-AS1 expression.

Conclusion: HAND2-AS1 effectively distinguished OA patients from the healthy controls and regulates IL‐6 expression in human chondrocytes.

Abbreviations: Long non-coding RNA, lncRNA; Osteoarthritis, OA; Interleukin 6, IL‐6; Negative control plasmid, NC; Real‐time quantitative polymerase chain reaction, qRT-PCR; Enzyme‐linked immunosorbent assay, ELISA; Receiver operating characteristic curve, ROC;

Trial registration: ChiCTR, ChiCTR2000038635. Registered 11 February 2019, http:// http://www.chictr.org.cn/ ChiCTR2000038635