LINC01534/miR-135b-5p/PTPRT axis regulates inflammatory response in loosening total hip replacement via modulating NF-κB signaling pathway. Issue 6 (June 2022)

• Record Type: Journal Article
• Authors: Zhang, Yaling; Zhu, Qingsheng; Fang, Qing; Yin, Dayu; Duan, Yonghong; Xue, Gang; Ma, Nan; Cai, Yuanzhen; He, Ming
• Is Part Of: Injury. Volume 53:Issue 6(2022)
• Page Start: 1829
• Page End: 1836
• Publication Date: 2022-06
• Subjects: LINC01534 -- miR-135b-3p -- CNBP -- Osteolysis -- Chondrocytes; THR Total hip replacement -- LncRNA Long non-coding RNAs; Wounds and injuries -- Surgery -- Periodicals; Accidents -- Periodicals; Wounds and Injuries -- surgery -- Periodicals; Lésions et blessures -- Chirurgie -- Périodiques; Electronic journals; Electronic journals; 617.1
• DOI: 10.1016/j.injury.2022.03.022
• Languages: English
• ISSNs: 0020-1383

Abstract

Abstract: Aseptic loosening after total hip replacement brings adverse health outcomes and increased risk for complications. The resorptive activity of inflammatory cells activated by the presence of wear-generated debris plays a critical role in debris-induced osteolysis. Previous studies indicate that the abnormally expressed LINC01534 plays a critical role in inflammatory responses. In this study, we aimed to elucidate the functional role and underlying mechanism of LINC01534 in debris-induced osteolysis. We first confirmed that LINC01534 was highly expressed in hip cartilage tissues from aseptic loosening patients. By using an IL-1β-induced inflammation model mimicking debris-induced osteolysis, we demonstrated that LINC01534 promoted IL-1β-induced inflammatory response in hip chondrocytes. Knockdown of LINC01534 inhibited the expression of inflammatory IL-6, IL-8, and TNF-α in hip chondrocytes. Our results showed that LINC01534 functioned as a competing endogenous RNA (ceRNA) by sponging miR-135b-5p in hip chondrocytes. Moreover, bioinformatics analysis and luciferase reporter assay demonstrated that CCHC-Type Zinc Finger Nucleic Acid Binding Protein (PTPRT) is a downstream target of miR-135b-5p. Knockdown of PTPRT attenuated the IL-1β-induced inflammatory responses in hip chondrocytes. In addition, we revealed that inhibition of miR-135b-5p or overexpression of PTPRT could antagonize the effects of LINC01534 knockdown on inflammation attenuation in hip chondrocytes. Mechanistically, we demonstrated that LINC01534/miR-135b-5p/PTPRT axis regulated the NF-κB signaling pathway in hip chondrocytes. Taken together, our findings suggest that LINC01534/miR-135b-5p/PTPRT axis might be a valuable therapeutic target for the treatment of debris-induced osteolysis.