Osteoarthritis (OA) affects more than 600 million people worldwide, yet no disease-modifying OA drug exists and most patients ultimately require joint replacement. Long regarded as a local, age-related “wear-and-tear” disease of cartilage, OA is increasingly recognized as a systemic disorder in which the whole-body metabolic and inflammatory milieu drives its onset and progression. In particular, adipose tissue is not merely a mechanical load but actively drives OA structural damage and pain through adipokines such as leptin. Likewise, the gut–joint axis, whereby gut microbial dysbiosis influences joint tissues through systemic inflammation and circulating metabolites, has emerged as a promising therapeutic target.
Based on these insights, this study hypothesizes that systemic factors derived from adipose tissue and the gut microbiota act on knee joint tissues—cartilage and meniscus—to govern OA onset and progression.
 This project aims to (1) integrate multi-omics data—gut microbiome, plasma metabolome, and joint tissues—to elucidate the molecular mechanisms by which systemic factors act on knee joint tissues, and (2) identify novel therapeutic candidates based on key metabolites and target molecules. By integrating orthopaedics with microbiology, metabolism, and drug discovery, this work seeks to establish a new paradigm for OA treatment.