Unraveling the mechanisms of bone diseases: targeting dendritic cells in osteoimmunology for internal homeostasis balance.

Bone repair and regeneration is a complex spatiotemporal process recruiting a variety of cell types, which need to precisely mediated for effective healing post-damage. The concept of osteoimmunology emphasizes the extensive and intricate crosstalk between the bone and the immune system. Despite the significant advancements in understanding osteoimmunology, the precise role of dendritic cells (DCs) in this field remains under investigation. As key antigen-presenting cells, DCs are critical in orchestrating adaptive immune responses and maintaining tissue homeostasis. Recent researches have further revealed the potential of DCs to influence the development or acceleration of inflammatory and autoimmune bone disease, as well as their interaction with skeletal cells in the context of bone repair and regeneration. Therefore, an in-depth understanding of DCs in the osteoimmunology would be valuable. Herein, we discuss the effects of DCs on bone homeostasis and bone-related diseases (i.e., rheumatoid arthritis (RA), periodontitis, bone regeneration, and other bone abnormalities diseases), and introduce the innovative DCs-targeting biomaterials, aimed at promoting bone repair and regeneration. Furthermore, we summarize the underlying crosstalk between DCs and other cells (i.e., osteoclasts, mesenchymal stromal stem cells (MSCs), hematopoietic stem and progenitor cells (HSPCs), T and B cells) in the bone homeostasis and bone-related diseases. In conclusion, we propose that osteoimmunology offers a promising perspective for unraveling the mechanisms of bone-related diseases; meanwhile, targeting DCs from the perspective of osteoimmunology may provide innovative ideas and resolutions to achieve the internal homeostasis balance.