Osteoarthritis (OA) is the most prevalent musculoskeletal disease in elderly people. Hand OA particularly affects women. A subtype of hand OA, the erosive type, is characterized by a more inflammatory pattern and presence of subchondral erosions and more destructive lesions. The ultimate treatment goal of OA should be structure modification. The search for efficacious treatments has been hampered by limited knowledge of responsible immune pathways. The goal of this project is to deepen our understanding of the underlying pathophysiology and better define key molecular processes driving this disease, in specific the RANK/RANKL/OPG pathway, and identify a specific synovial fibroblast subset that aggravates osteoclastogenesis and development of bone erosions. Critical novel concepts are the integration of molecular research with well-defined patient samples, i.e. synovial tissue biopsies, and use of cutting-edge next generation sequencing technologies for biomarker discovery.