MiRNA-132 regulates the development of osteoarthritis in correlation with the modulation of PTEN/PI3K/AKT signaling

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Abstract

Background

Osteoarthritis (OA) is a commonly known prevalent joint disease, with limited therapeutic methods. This study aimed to investigate the functions of miRNA-132 (miR-132) in the modulation of PTEN/PI3K/AKT signaling pathway in the development and progression of osteoarthritis.

Methods

Eight male osteoarthritic patients and eight healthy males were recruited. Male Sprague Dawley (SD) rats were used for cellular experiments. QRT-PCR was performed to detect the expression levels of miR-132, PTEN, PI3K and AKT. MTT assay and apoptosis assay were carried out to measure the cell proliferation rate and cell apoptosis rate, respectively. Western blotting was employed to detect the protein expression of related RNAs and inflammatory factors.

Results

In osteoarthritic patients, the expression level of miR-132 was decreased, compared with that in the normal group. Over-expression of miR-132 elevated cell proliferation and decreased apoptosis of chondrocytes. Down-regulation of miR-132 decreased cell proliferation and induced apoptosis in chondrocytes. In addition, down-regulation of miR-132 promoted the expression of Bax protein and activated caspase-3/9, increased inflammation divisors. PTEN inhibitor antagonized the destructive effect of the miR-132 inhibitor on cell proliferation of chondrocytes. PI3K inhibitor increased the destructive effect of the miR-132 inhibitor on osteoarthritis.

Conclusion

In conclusion, miR-132 is an important regulator of osteoarthritis in chondrocytes through the PTEN/PI3K/AKT signaling pathway.

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Most cited references 36

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Knee Injury and Osteoarthritis Outcome Score (KOOS)--development of a self-administered outcome measure.

E M Roos, H. P. Roos, L S Lohmander … (1998)

There is broad consensus that good outcome measures are needed to distinguish interventions that are effective from those that are not. This task requires standardized, patient-centered measures that can be administered at a low cost. We developed a questionnaire to assess short- and long-term patient-relevant outcomes following knee injury, based on the WOMAC Osteoarthritis Index, a literature review, an expert panel, and a pilot study. The Knee injury and Osteoarthritis Outcome Score (KOOS) is self-administered and assesses five outcomes: pain, symptoms, activities of daily living, sport and recreation function, and knee-related quality of life. In this clinical study, the KOOS proved reliable, responsive to surgery and physical therapy, and valid for patients undergoing anterior cruciate ligament reconstruction. The KOOS meets basic criteria of outcome measures and can be used to evaluate the course of knee injury and treatment outcome.

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Animal MicroRNAs confer robustness to gene expression and have a significant impact on 3'UTR evolution.

Alexander Stark, Julius Brennecke, Natascha Bushati … (2005)

MicroRNAs are small noncoding RNAs that serve as posttranscriptional regulators of gene expression in higher eukaryotes. Their widespread and important role in animals is highlighted by recent estimates that 20%-30% of all genes are microRNA targets. Here, we report that a large set of genes involved in basic cellular processes avoid microRNA regulation due to short 3'UTRs that are specifically depleted of microRNA binding sites. For individual microRNAs, we find that coexpressed genes avoid microRNA sites, whereas target genes and microRNAs are preferentially expressed in neighboring tissues. This mutually exclusive expression argues that microRNAs confer accuracy to developmental gene-expression programs, thus ensuring tissue identity and supporting cell-lineage decisions.

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The Knee injury and Osteoarthritis Outcome Score (KOOS): from joint injury to osteoarthritis

Ewa Roos, Stefan Lohmander (2004)

The Knee injury and Osteoarthritis Outcome Score (KOOS) was developed as an extension of the WOMAC Osteoarthritis Index with the purpose of evaluating short-term and long-term symptoms and function in subjects with knee injury and osteoarthritis. The KOOS holds five separately scored subscales: Pain, other Symptoms, Function in daily living (ADL), Function in Sport and Recreation (Sport/Rec), and knee-related Quality of Life (QOL). The KOOS has been validated for several orthopaedic interventions such as anterior cruciate ligament reconstruction, meniscectomy and total knee replacement. In addition the instrument has been used to evaluate physical therapy, nutritional supplementation and glucosamine supplementation. The effect size is generally largest for the subscale QOL followed by the subscale Pain. The KOOS is a valid, reliable and responsive self-administered instrument that can be used for short-term and long-term follow-up of several types of knee injury including osteoarthritis. The measure is relatively new and further use of the instrument will add knowledge and suggest areas that need to be further explored and improved.

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Author and article information

Contributors

Xiaowei Yu: yuxw@sjtu.edu.cn

Journal

Journal ID (nlm-ta): BMC Geriatr

Journal ID (iso-abbrev): BMC Geriatr

Title: BMC Geriatrics

Publisher: BioMed Central (London )

ISSN (Electronic): 1471-2318

Publication date (Electronic): 10 March 2021

Publication date PMC-release: 10 March 2021

Publication date Collection: 2021

Volume: 21

Electronic Location Identifier: 175

Affiliations

GRID grid.412528.8, ISNI 0000 0004 1798 5117, Department of Orthopaedics, , Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, ; No. 600 Yishan Road, Shanghai, 200233 China

Article

Publisher ID: 2046

DOI: 10.1186/s12877-021-02046-8

PMC ID: 7945330

PubMed ID: 33691628

SO-VID: 9f8ea26f-988b-4468-9c11-dc12592cd031

License:

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

History

Date received : 14 January 2020

Date accepted : 21 January 2021

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ScienceOpen disciplines: Geriatric medicine

Keywords: mir-132,osteoarthritis,chondrocytes,pten/pi3k/akt signaling pathway

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ScienceOpen disciplines: Geriatric medicine

Keywords: mir-132, osteoarthritis, chondrocytes, pten/pi3k/akt signaling pathway

MiRNA-132 regulates the development of osteoarthritis in correlation with the modulation of PTEN/PI3K/AKT signaling

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Abstract

Background

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Conclusion

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Neuronal Signaling

Most cited references 36

Knee Injury and Osteoarthritis Outcome Score (KOOS)--development of a self-administered outcome measure.

Animal MicroRNAs confer robustness to gene expression and have a significant impact on 3'UTR evolution.

The Knee injury and Osteoarthritis Outcome Score (KOOS): from joint injury to osteoarthritis

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