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Circulating microRNAs differentiate fast-progressing from slow-progressing and non-progressing knee osteoarthritis in the Osteoarthritis Initiative cohort.


ABSTRACT:

Introduction

The objective of this study is to identify circulating microRNAs that distinguish fast-progressing radiographic knee osteoarthritis (OA) in the Osteoarthritis Initiative cohort by applying microRNA-sequencing.

Methods

Participants with Kellgren-Lawrence (KL) grade 0/1 at baseline were included (N = 106). Fast-progressors were defined by an increase to KL 3/4 by 4-year follow-up (N = 20), whereas slow-progressors showed an increase to KL 2/3/4 only at 8-year follow-up (N = 35). Non-progressors remained at KL 0/1 by 8-year follow-up (N = 51). MicroRNA-sequencing was performed on plasma collected at baseline and 4-year follow-up from the same participants. Negative binomial models were fitted to identify differentially expressed (DE) microRNAs. Penalized logistic regression (PLR) analyses were performed to select combinations of DE microRNAs that distinguished fast-progressors. Area under the receiver operating characteristic curves (AUC) were constructed to evaluate predictive ability.

Results

DE analyses revealed 48 microRNAs at baseline and 2 microRNAs at 4-year follow-up [false discovery rate (FDR) < 0.05] comparing fast-progressors with both slow-progressors and non-progressors. Among these were hsa-miR-320b, hsa-miR-320c, hsa-miR-320d, and hsa-miR-320e, which were predicted to target gene families, including members of the 14-3-3 gene family, involved in signal transduction. PLR models included miR-320 members as top predictors of fast-progressors and yielded AUC ranging from 82.6 to 91.9, representing good accuracy.

Conclusion

The miR-320 family is associated with fast-progressing radiographic knee OA and merits further investigation as potential biomarkers and mechanistic drivers of knee OA.

SUBMITTER: Ali SA 

PROVIDER: S-EPMC8935408 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Circulating microRNAs differentiate fast-progressing from slow-progressing and non-progressing knee osteoarthritis in the Osteoarthritis Initiative cohort.

Ali Shabana Amanda SA   Espin-Garcia Osvaldo O   Wong Andy K AK   Potla Pratibha P   Pastrello Chiara C   McIntyre Madison M   Lively Starlee S   Jurisica Igor I   Gandhi Rajiv R   Kapoor Mohit M  

Therapeutic advances in musculoskeletal disease 20220318


<h4>Introduction</h4>The objective of this study is to identify circulating microRNAs that distinguish fast-progressing radiographic knee osteoarthritis (OA) in the Osteoarthritis Initiative cohort by applying microRNA-sequencing.<h4>Methods</h4>Participants with Kellgren-Lawrence (KL) grade 0/1 at baseline were included (<i>N</i> = 106). Fast-progressors were defined by an increase to KL 3/4 by 4-year follow-up (<i>N</i> = 20), whereas slow-progressors showed an increase to KL 2/3/4 only at 8-y  ...[more]

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