Abstract
Osteoarthritis (OA) is a chronic joint disease and hard to cure at present. Accumulating evidence suggests long noncoding RNA-HOTAIR (lncRNA-HOTAIR) plays important role in OA progression. However, the underlying molecular mechanism of HOTAIR in OA progression has not been well elucidated. In the present study, we identified that HOTAIR level was upregulated in OA cartilage tissues. High expression of HOTAIR was correlated with modified Mankin scale, extracellular matrix (ECM) degradation and chondrocytes apoptosis. The expression of miR-17-5p was down-regulated, while alpha-1, 2 fucosyltransferase 2 (FUT2) was increased in OA progression. Luciferase reporter and RNA immunoprecipitation (RIP) assays indicated that HOTAIR could directly bind to miR-17-5p and indirectly upregulate FUT2 level. Functional investigation revealed HOTAIR and FUT2 aggravated ECM degradation and chondrocytes apoptosis, and this effect could be reversed by miR-17-5p. Altered FUT2 modulated the activity of wnt/β-catenin pathway and HOTAIR/miR-17-5p also mediated wnt/β-catenin pathway through FUT2. Collectively, our findings indicated that HOTAIR/miR-17-5p/FUT2 axis contributed to OA progression via wnt/β-catenin pathway, which might provide novel insights into the function of lncRNA-driven in OA.
Highlights
Osteoarthritis (OA) is characterized by the destruction of articular cartilage, which is mainly due to the imbalance of extracellular matrix components such as type ⍺ collagen and proteoglycan
More and more researchers noticed that lncRNAs play important roles in OA progression
Several lncRNAs were identified to contribute to OA progression, including GAS5, PCGEM1, lncRNA-CIR and HOTAIR25–27
Summary
Osteoarthritis (OA) is characterized by the destruction of articular cartilage, which is mainly due to the imbalance of extracellular matrix components such as type ⍺ collagen and proteoglycan. The degradation of extracellular matrix is mainly owning to the activation of matrix metalloproteinase (MMPs) and a disintegrin and metalloproteinase domain with thrombospondin motifs family (ADAMTSs) proteins[1,2]. Long non-coding RNAs (lncRNAs) are a series of over 200 nucleotides noncoding endogenous RNAs, which have been confirmed to play important roles in the development of inflammation-related diseases[5]. More and more evidence demonstrated that lncRNAs were involved in cell biological processes including cell proliferation and apoptosis, cellular differentiation, tumorigenesis, and metastasis[6,7]. MicroRNAs (miRNAs), a series of small noncoding RNAs with 18–22 nt in length, have been reported in inflammation-related diseases[8]. HOTAIR promoted cell proliferation, cell cycle progression, invasion and malignancy by Official journal of the Cell Death Differentiation Association
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
