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miR-140-5p/miR-149 Affects Chondrocyte Proliferation, Apoptosis, and Autophagy by Targeting FUT1 in Osteoarthritis

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Abstract

Osteoarthritis (OA), the most prevalent chronic and degenerative joint disease, is characterized by articular cartilage degradation and chondrocyte injury. Increased cell apoptosis and defective cell autophagy in chondrocytes are a feature of degenerative cartilage. MicroRNAs (miRNAs) have been identified as potential regulators of OA. This study aimed to determine the potential role of miR-140-5p and miR-149 in apoptosis, autophagy, and proliferation in human primary chondrocytes and investigate the underlying mechanism. We revealed the differential expressional profiles of miR-140-5p/149 and fucosyltransferase 1 (FUT1) in the articular cartilage tissues of OA patients and normal people and validated FUT1 was a direct target of miR-140-5p/149. The overexpression of miR-140-5p/149 inhibited apoptosis and promoted proliferation and autophagy of human primary chondrocytes via downregulating FUT1. On the contrary, the downregulation of miR-140-5p/149 inhibited chondrocyte proliferation and autophagy, whereas the effect was reversed by FUT1 knockdown. Taken together, our data suggested that miR-140-5p and miR-149 could mediate the development of OA, which was regulated by FUT1. miR-140-5p/miR-149/FUT1 axis might serve as a predictive biomarker and a potential therapeutic target in OA treatment.

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Change history

  • 22 March 2019

    The original version of this article contained mistakes, and the authors would like to correct them.

  • 22 March 2019

    The original version of this article contained mistakes, and the authors would like to correct them.

Abbreviations

3′-UTR:

3′-Untranslated region

OA:

Osteoarthritis

miRNAs:

MicroRNAs

siRNA:

Small interfering RNA

PBS:

Phosphate-buffered saline

BSA:

Bovine serum albumin

FUT1:

Fucosyltransferase 1

GVA:

Glycerol vinyl alcohol aqueous

FITC:

Fluorescein isothiocyanate

PI:

Propidium iodide

DAPI:

4′,6-Diamidino-2-phenylindole

BCA:

Bicinchoninic acid

HRP:

Horseradish peroxidase

CCK-8:

Cell Counting Kit-8

EDU:

5-Ethynyl-2′-deoxyuridine

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Funding

This work was supported by grants from the National Natural Science Foundation of China (81472014, 81772277).

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Correspondence to Li Jia.

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This research was approved by the Research Ethics Committee of Dalian Municipal Central Hospital and Dalian Medical University. All participants signed the informed consents.

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The authors declare that they have no conflict of interest.

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Wang, Z., Hu, J., Pan, Y. et al. miR-140-5p/miR-149 Affects Chondrocyte Proliferation, Apoptosis, and Autophagy by Targeting FUT1 in Osteoarthritis. Inflammation 41, 959–971 (2018). https://doi.org/10.1007/s10753-018-0750-6

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  • DOI: https://doi.org/10.1007/s10753-018-0750-6

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