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.

Analysis of RNA Polyadenylation in Healthy and Osteoarthritic Human Articular Cartilage

“…They are polyadenylated and so our inability to fully characterise them in our samples represents a limitation of the study. Interestingly, among the small RNAs that we were able to detect were potential biomarkers for osteoarthritis, such as miR-320d [ 29 ] and SNORD13 [ 30 ].…”

Analysis of RNA polyadenylation in healthy and osteoarthritic human articular cartilage

“…They are polyadenylated and so our inability to fuilly charaterise them in our samples represent a limitation of the study. Interestingly, among the small RNAs that we were able to detect were potential biomarkers for osteoarthritis, such as miR-320d [39] and SNORD13 [40].…”

Emerging molecular biomarkers in osteoarthritis pathology

“…50 Furthermore, in a KOA patient sample from the Osteoarthritis Initiative (OAI) cohort ( n = 106), an association was found between plasma levels of the miR-320 family (miR-320b/c/d/e) and fast-progressing radiographic KOA subjects over a 4-year period. 51 Finally, in a sample of KOA patients (KL II-IV, n = 136), baseline levels of 3 miRNAs (miR-146a-5p, miR-145-5p, and miR-130b-3p) were higher in individuals with lower pain relief, with mir-146a-5p trending as an independent predictor of postoperative pain relief. 52 Taken together, these findings suggest that miRNAs may act as important predictors of OA progression.…”