Significant Changes in Serum MicroRNAs after High Tibial Osteotomy in Medial Compartmental Knee Osteoarthritis: Potential Prognostic Biomarkers

Abstract

High tibial osteotomy (HTO) is an effective alternative for medial compartmental knee osteoarthritis (OA). Circulating microRNAs (miRNAs) are known to serve as OA-related biomarkers. The present study investigated the differential expression of serum miRNAs before and after HTO to identify potential miRNAs as prognostic biomarkers. miRNA-polymerase chain reaction (PCR) arrays were used to screen for miRNAs in the serum at preoperative and 6-month postoperative time points from six patients, and the differentially expressed miRNAs identified in the profiling stage were validated using real-time PCR at post-operative months 6 and 18 in 27 other HTO-treated patients. Among 84 miRNAs involved in the inflammatory process, three (miR-19b-3p, miR-29c-3p, and miR-424-5p) showed differential expression patterns in the profiling stage (p = 0.011, 0.015, and 0.021, respectively). Levels of these three and four other miRNAs (miR-140-3p, miR-454-3p, miR-let-7e-5p, and miR-885-5p) known to be related to OA progression were evaluated in the serum of 27 patients. Only four miRNAs (miR-19b-3p, miR-140-3p, miR-454-3p, and miR-let-7e-5p) were significantly upregulated at postoperative month 6 (p = 0.003, 0.005, 0.004, and 0.004, respectively), and only miR-140-3p was significantly upregulated up to 18 months after operation (p = 0.003). Together, this study reveals the significantly upregulated serum miRNAs after HTO as potential prognostic biomarkers; however, further studies are warranted to elucidate their clinical implications.

Exosomes from osteoarthritic fibroblast-like synoviocytes promote cartilage ferroptosis and damage via delivering microRNA-19b-3p to target SLC7A11 in osteoarthritis

“…In line with our previous study (25), the present study observed that miR-19b-3p was higher in cartilage tissues of OA patients and elevated in IL-1bstimulated chondrocytes (OA cellular model) as well as in cartilage tissues of OA rat models. These data further validated the miR-19b-3p involvement in OA development, which might be ascribed to the effect of miR-19b-3p on regulating chondrocyte functions, ECM degradation, and inflammation (44)(45)(46). Importantly, our present study also discovered that OA-FLS exosomes promote the damage and ferroptosis of chondrocyte and cartilage via delivering miR-19b-3p in vitro and in vivo, respectively.…”

“…miR-19b-3p is a famous noncoding RNA involved in the pathogenesis of various diseases such as cancers, skeletal abnormalities, and degenerative diseases (41)(42)(43). In the aspect of OA, miR-19b-3p is reported to regulate ECM degradation and inflammation in OA (44), and its change during/post-treatment relates to OA recovery (45). Moreover, our previous study used microarray and RT-qPCR assay to confirm that miR-19b-3p was elevated in knee OA patients compared to healthy controls, which was further revealed to be an independent risk factor for OA susceptibility (25).…”

“…Importantly, our present study also discovered that OA-FLS exosomes promote the damage and ferroptosis of chondrocyte and cartilage via delivering miR-19b-3p in vitro and in vivo, respectively. These might result from the effect of miR-19b-3p on oxidative stress, inflammation, and direct ferroptosis and its abundant contents in OA-FLS exosomes (44)(45)(46)(47)(48)(49).…”

miR-140-5p and miR-140-3p: Key Actors in Aging-Related Diseases?

“…miR-140-3p level has been monitored in the serum from OA patients before and after high tibial osteotomy (HTO), which represents one option for OA-treatment, as cartilage regeneration is expected after this surgery. miR-140-3p expression is significantly up-regulated 6 and 18 months post-surgery, indicating that the miR-140-3p seric level may represent a prognostic biomarker for the cartilage repair process [ 107 ].…”

LncRNA H19 Influences Cellular Activities via the miR-454-3p/BHLHE40 Axis in Anaplastic Thyroid Carcinoma

“…Existing literature has demonstrated that lncRNA H19 competitively binds to miR-454-3p and other miRNAs and regulates their expression in colorectal carcinoma [11]. Notably, the expression of miR-454-3p was linked with various diseases and could act in crucial roles by targeting mRNAs [12][13][14]. The basic-helix-loop-helix (BHLH) protein BHLHE40 (also named BHLHB2, STRA13, DEC1, or SHARP2) was involved in numerous diseases [15,16].…”