# MiRNA-Mediated Regulation in Osteoarthritis Across Joint Tissues, Including Translational Perspectives in Dogs

## TL;DR

This paper reviews how microRNAs (miRNAs) regulate joint tissues in osteoarthritis (OA) in humans and dogs, highlighting their potential as non-invasive biomarkers and the need for more research in canine OA.

## Contribution

The paper introduces a comparative framework for miRNA research in human and canine OA, emphasizing translational potential and shared molecular contexts.

## Key findings

- miRNAs regulate joint inflammation, cartilage breakdown, and bone remodeling in human OA.
- Dogs naturally develop OA similar to humans, making them a valuable model for miRNA studies.
- Only one pilot study has investigated miRNA expression in spontaneous canine OA, revealing significant research gaps.

## Abstract

Osteoarthritis (OA) is a common joint disease in both humans and dogs that causes pain, reduced mobility, and gradual loss of joint function. Although it has traditionally been viewed as a cartilage problem, OA actually involves the entire joint, including bone, synovium, and surrounding tissues that communicate with each other during disease progression. As life expectancy has increased in both humans and dogs, the prevalence of OA has risen substantially, making it an increasingly relevant health problem in aging populations. At the molecular level, epigenetic mechanisms help shape how joint tissues respond to mechanical stress, inflammation, and aging. Among these mechanisms, microRNAs (miRNAs) are small molecules that regulate how genes work inside cells and can also be released into body fluids such as blood and joint fluid. Growing evidence from human studies shows that miRNAs play a key role in joint inflammation, cartilage breakdown, bone remodeling, and cell survival. Because they can circulate in stable forms, miRNAs are also being investigated as potential non-invasive biomarkers of joint disease. Dogs naturally develop OA in a way that closely resembles the human condition, making them a valuable model for comparative research. However, miRNA studies in canine OA are still very limited. This review summarizes current knowledge on miRNAs in human OA and highlights how these findings can guide future research in dogs to improve diagnosis, monitoring, and ultimately treatment of osteoarthritis in both species.

Osteoarthritis (OA) is increasingly conceptualized as a whole-joint disorder, in which pathological processes across articular cartilage, subchondral bone, synovium, and periarticular tissues are tightly interconnected. Within this context, miRNAs have emerged as central post-transcriptional regulators capable of integrating mechanical, inflammatory, and metabolic cues at the network level. In human OA, extensive evidence links miRNA dysregulation to cartilage catabolism, impaired stress adaptation, inter-tissue communication, and the emergence of extracellular and circulating miRNA (cmiRNA) signatures with diagnostic and translational relevance. In contrast, miRNA research in canine OA remains limited, despite dogs developing a naturally occurring form of the disease that closely mirrors human OA in clinical presentation, joint pathology, and biomechanical drivers. To date, only a single pilot study has systematically investigated miRNA expression in spontaneous canine OA, underscoring both the feasibility of miRNA profiling and the substantial gaps that persist in tissue validation and functional characterization. This review critically synthesizes miRNA-mediated regulatory mechanisms in human OA and leverages this evidence to define research priorities in canine OA, where experimental validation remains limited. By focusing on shared molecular contexts rather than assumed equivalence, the review defines a comparative framework highlighting cmiRNAs as promising non-invasive translational targets.