Osteoarthritis (OA) is the most common joint disorder, affecting over 300 million people worldwide [1]. The knee joint is a typical joint that develops OA, which is known to cause pain, deformity, and a reduction in daily activities [2]. Althogh many studies suggest that conservative treatment is effective in cases of mild knee OA (KOA) [3], as the disease progresses to the late stages, total knee arthroplasty becomes the first choice of treatment [4]. The ability to predict the progression of KOA and avoid surgery through preventive medicine is critical for patients and health care costs [5] (see Table 3) (Table 3).

Many factors that predict the progression of KOA have been identified [6], with microRNAs (miRNAs) receiving current attention as a predictor of OA [[7], [8], [9]]. MiRNAs are single-stranded, non-coding RNA molecule containing small 20–25 nucleotides found in plants, animals, and some viruses that function in RNA silencing and post-transcriptional regulation of gene expression [10]. Recent studies have shown that circulating miRNAs (c-miRNAs) may be stable because they are protected by exosomes and can reflect the state of the lesion and its specificity for the damaged tissue [11].

Cancer and other diseases use c-miRNAs as biomarkers [12]. Several studies have reported the association between c-miRNAs and KOA [9]. However, c-miRNAs have not yet been identified as predictors of KOA progression based on longitudinal evaluation of KOA.

We hypothesized that c-miRNAs could be predictors of KOA in humans. Thus, the study aimed to evaluate whether c-miRNAs can predict KOA progression prospectively in community-dwelling Japanese people.