Core Regulatory RNA Molecules Identified in Articular Cartilage Stem/Progenitor Cells During Osteoarthritis Progression

Abstract

<b>Aim:</b> To assess cartilage-derived stem/progenitor cells (CSPCs) in osteoarthritis (OA) by employing mRNA-miRNA-circRNA-lncRNA network biology approach. <b>Methods:</b> Differentially expressed (DE) RNAs in CSPCs from 2-/4-/8-month-old STR/Ort and CBA mice were identified to construct networks via RNA sequencing. <b>Results:</b> Compared with age-matched CBA mice, 4-/8-month-old STR/Ort mice had cartilage lesions and their CSPCs exhibited lower proliferative and differentiation capacity (decreased CD44 and CD90), and identified 7082 DE RNAs in STR/Ort mice were associated with strain differences or OA progression. OA-related core RNAs were identified via the networks constructed with the predominant DE RNAs, which were involved in the signaling pathways (NF-κB/MAPK/Hippo/Wnt/TGF-β/cytoskeleton organization). The core RNAs (miR-322-5p/miR-493-5p/miR-378c/<i>CPNE1/Cdh2/PRDM16/CTGF/NCAM1</i>) were validated in CSPCs from OA patients. <b>Conclusion:</b> RNA-based networks identifying core RNAs and signaling pathways contribute to CSPC-dependent OA mechanisms.