Updating the pathophysiology of arthritic bone destruction: identifying and visualizing pathological osteoclasts in...

Osteoclasts have a unique capacity to destroy bone, playing key roles in physiological bone remodeling and arthritic bone erosion. It is not known whether the osteoclast populations in different tissue settings arise from similar monocytoid precursors. The rapid progress in the next-generation sequencing technologies has provided many valuable insights into the field of osteoimmunology, and single-cell RNA sequencing (scRNA-Seq) can elucidate cellular heterogeneity within the synovial microenvironment. The application of scRNA-Seq to the defined osteoclast precursor (OP)-containing population enabled the identification of individual cells differentiating into mature osteoclasts in the inflamed synovium, which were distinct from conventional OPs in the bone marrow. In addition, an intravital imaging system using multi-photon microscopy has been applied to the synovial tissues of arthritic mice to observe the real-time dynamics of osteoclasts and immune cells in the pannus. These technologies have contributed to elucidate the transcriptomics and dynamics of specific cells involved in pathological osteoclastogenesis, improving our understand of the pathophysiology of inflammatory osteolytic diseases. Here, we review how novel technologies such as scRNA-Seq and intravital imaging help to better understand the pathogenesis of bone erosion and we introduce recent studies that have identified and directly visualized pathological OPs in inflamed synovium.