MicroRNAs as Key Regulators of Degeneration and Inflammation in Osteoarthritis: A Narrative Review
TL;DR
Current evidence on the roles of miRNAs in OA is synthesized, focusing on their regulatory functions across joint tissues, including cartilage, synovium, subchondral bone, and the infrapatellar fat pad, along with their interactions with major inflammatory and degenerative signaling pathways.
Abstract
Osteoarthritis (OA) is the most prevalent degenerative joint disease and a leading cause of chronic pain and disability worldwide, particularly among aging populations. It is characterized by progressive degeneration of articular cartilage, synovial inflammation, subchondral bone remodeling, and metabolic alterations in the infrapatellar fat pad, reflecting pathology across the entire joint microenvironment. The onset and progression of OA are driven by complex interactions among mechanical stress, aging, obesity, and metabolic dysregulation, which collectively disrupt joint homeostasis. Mechanical injury and cartilage damage induce the release of damage-associated molecular patterns, activating innate immune receptors on chondrocytes and synovial cells. This promotes the production of pro-inflammatory mediators, including interleukin-1β, tumor necrosis factor-α (TNF-α), interleukin-6, and interleukin-17, which contribute to extracellular matrix degradation and cartilage deterioration. MicroRNAs (miRNAs), small non-coding RNAs that regulate gene expression post-transcriptionally, have emerged as key modulators in OA pathogenesis. They regulate chondrocyte proliferation, apoptosis, extracellular matrix turnover, inflammation, and osteochondral remodeling. Notably, certain miRNAs exhibit mechanosensitive properties, responding to altered biomechanical loading and translating mechanical stimuli into gene regulatory responses. This review synthesizes current evidence on the roles of miRNAs in OA, focusing on their regulatory functions across joint tissues, including cartilage, synovium, subchondral bone, and the infrapatellar fat pad. Key miRNAs such as miR-140, miR-146a, miR-27b, miR-34a, miR-155, and mechanosensitive miR-365 are discussed, along with their interactions with major inflammatory and degenerative signaling pathways. Their potential as diagnostic biomarkers and therapeutic targets is also highlighted.