Erosive hand osteoarthritis (EHOA) is a unique subset of osteoarthritis (OA), characterized by destructive subchondral erosions and is associated with severe pain and an impaired hand function. The occurrence of these radiographically defined erosions, are a distinct feature differentiating EHOA from all other non-erosive OA types. Until now, the molecular mechanisms driving structural damage in hand OA and particularly EHOA are poorly understood, resulting in an unmet medical need for effective treatments. Our research team has recently conducted a clinical trial with a RANKL-inhibitor, potentially causing a drastic change in EHOA treatment. Moreover, we confirmed a salient role for RANKL in human tissue samples. Our rheumatology clinic recently introduced a new technique of synovial tissue biopsy under ultrasound guidance, expanding our access to unique finger biopsies from EHOA patients for molecular research. This project aims to deepen our understanding of the underlying molecular mechanisms of the distinct features of the erosive phenotype of hand OA by investigating the role of RANKL in the crosstalk between synovial fibroblasts and synovial myeloid cells in EHOA. This proposal will introduce a novel concept in the research field of hand OA by combining molecular research techniques with unique synovial finger biopsies from a well-defined cohort.