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BMC Musculoskeletal Disorders
Published in: BMC Musculoskeletal Disorders 1/2021

01-12-2021 | Osteoarthrosis | Research article

LncRNA HOTTIP leads to osteoarthritis progression via regulating miR-663a/ Fyn-related kinase axis

Authors: Xianwei He, Kun Gao, Shuaihua Lu, Rongbo Wu

Published in: BMC Musculoskeletal Disorders | Issue 1/2021

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Abstract

Background

Long non-coding RNA (lncRNA) has been implicated in the progression of osteoarthritis (OA). This study was aimed to explore the role and molecular mechanism of lncRNA HOXA terminal transcriptional RNA (HOTTIP) in the development of OA.

Methods

The expression of HOTTIP, miR-663a and Fyn-related kinase (FRK) in the OA articular cartilage and OA chondrocyte model induced by IL-1β was determined by qRT-PCR. CCK-8, colony formation and flow cytometry were used to determine the cell proliferation and apoptosis of OA chondrocytes. The specific molecular mechanism of HOTTIP in OA chondrocytes was determined by dual luciferase reporter assay, qRT-PCR, western blotting and RNA pull-down.

Results

The expression of HOTTIP and FRK were up-regulated, while miR-663a was down-regulated in OA cartilage tissues. Knockdown of HOTTIP decreased the proliferation and induced the apoptosis of OA cartilage model cells, while overexpression of HOTTIP increased the proliferation and reduced the apoptosis of OA cartilage model cells. Moreover, HOTTIP could bind to miR-663a as competitive endogenous RNA. Inhibition of miR-663a expression could alleviate the effect of HOTTIP knockdown on the proliferation and apoptosis of OA cartilage model cells. Furthermore, FRK was found to be a direct target of miR-663a, which could markedly down-regulate the expression of FRK in OA chondrocytes, while HOTTIP could remarkably up-regulate the expression of FRK. In addition, miR-663a inhibition increased the proliferation and reduced the apoptosis of OA cells, while FRK knockdown reversed the effect of miR-663a inhibition on the proliferation and apoptosis of OA cells. Meanwhile, overexpression of miR-663a decreased the proliferation and induced the apoptosis of OA cells, while overexpression of FRK reversed the effect of miR-663a overexpression on the proliferation and apoptosis of OA cells.

Conclusion

HOTTIP was involved in the proliferation and apoptosis of OA chondrocytes via miR-663a/ FRK axis, and HOTTIP/miR-663a/FRK might be a potential target for the treatment of OA.
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Metadata
Title
LncRNA HOTTIP leads to osteoarthritis progression via regulating miR-663a/ Fyn-related kinase axis
Authors
Xianwei He
Kun Gao
Shuaihua Lu
Rongbo Wu
Publication date
01-12-2021
Publisher
BioMed Central
Published in
BMC Musculoskeletal Disorders / Issue 1/2021
Electronic ISSN: 1471-2474
DOI
https://doi.org/10.1186/s12891-020-03861-7

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