Dihydroartemisinin alleviates erosive bone destruction by modifying local Treg cells in inflamed joints: A novel role in the treatment of rheumatoid arthritis.

Treg cell-based therapy has exhibited promising efficacy in combatting rheumatoid arthritis (RA). Dihydroartemisinin (DHA) exerts broad immunomodulatory effects across various diseases, with its recent spotlight on T-cell regulation in autoimmune conditions. The modulation of DHA on Treg cells and its therapeutic role in RA has yet to be fully elucidated. This study seeks to unveil the influence of DHA on Treg cells in RA and furnish innovative substantiation for the potential of DHA to ameliorate RA. To this end, we initially scrutinized the impact of DHA-modulated Treg cells on osteoclast (OC) formation in vitro using Treg cell-bone marrow-derived monocyte (BMM) coculture systems. Subsequently, employing the collagen-induced arthritis (CIA) rat model, we validated the efficacy of DHA and probed its influence on Treg cells in the spleen and popliteal lymph nodes (PLN). Finally, leveraging deep proteomic analysis with data-independent acquisition (DIA) and parallel accumulation-serial fragmentation (PASEF) technology, we found the alterations in the Treg cell proteome in PLN by proteomic analysis. Our findings indicate that DHA augmented suppressive Treg cells, thereby impeding OC formation in vitro. Consistently, DHA mitigated erosive joint destruction and osteoclastogenesis by replenishing splenic and joint-draining lymph node Treg cells in CIA rats. Notably, DHA induced alterations in the Treg cell proteome in PLN, manifesting distinct upregulation of alloantigen Col2a1 (Type II collagen alfa 1 chain) and CD8a (T-cell surface glycoprotein CD8 alpha chain) in Treg cells, signifying DHA's targeted modulation of Treg cells, rendering them more adept at sustaining immune tolerance and impeding bone erosion. These results unveil a novel facet of DHA in the treatment of RA.

Mechanisms by which kidney-tonifying Chinese herbs inhibit osteoclastogenesis: Emphasis on immune cells.

The immune system plays a crucial role in regulating osteoclast formation and function and has significance for the occurrence and development of immune-mediated bone diseases. Kidney-tonifying Chinese herbs, based on the theory of traditional Chinese medicine (TCM) to unify the kidney and strengthen the bone, have been widely used in the prevention and treatment of bone diseases. The common botanical drugs are tonifying kidney-yang and nourishing kidney-yin herbs, which are divided into two parts: one is the compound prescription of TCM, and the other is the single preparation of TCM and its active ingredients. These botanical drugs regulate osteoclastogenesis directly and indirectly by immune cells, however, we have limited information on the differences between the two botanical drugs in osteoimmunology. In this review, the mechanism by which kidney-tonifying Chinese herbs inhibiting osteoclastogenesis was investigated, emphasizing the immune response. The differences in the mechanism of action between tonifying kidney-yang herbs and nourishing kidney-yin herbs were analysed, and the therapeutic value for immune-mediated bone diseases was evaluated.