The enhanced osteoclastogenesis contributes to alveolar bone resorption in periodontitis, which increases the risk of tooth loss. To reduce bone destruction, the inhibition of osteoclast development is proposed as a feasible treatment. CD40L-CD40-TRAF6 signal transduction plays a crucial role in inflammation, but how it regulates osteoclast activity in periodontitis has not been elucidated. In this study, we showed the potential role of CD40L-CD40-TRAF6 signaling in periodontitis. CD40L obviously promoted osteoclast formation and bone resorption capacity in vitro. Mechanistically, we found that osteoclastogenesis was enhanced by the overexpression of NFATc1 and NF-κB activation. Importantly, osteoclast activity was effectively suppressed by TRAF-STOP, a small molecular inhibitor of TRAF6. Furthermore, local injection of TRAF-STOP-loaded injectable PLGA-PEG-PLGA hydrogel could alleviate ligation-induced periodontitis in vivo. Taken together, TRAF-STOP shows promising clinical efficacy in periodontitis through alleviating osteoclastogenesis.
Agaricus bitorquis (QuéL.) Sacc. Chaidam is a valuable edible fungus in Qinghai-Tibet plateau and ABSP is a novel intracellular polysaccharide from its mycelia. GC and NMR analysis determined ABSP is galactoglucomannan-like polysaccharide that may have immunomodulatory effect. This study used RAW264.7 as model cell to determine immunomodulatory effect of ABSP. After ABSP treatment, viability and phagocytic ability promoted, and NO, ROS, TNF-α levels also raised which proved ABSP had immune regulation to RAW264.7. WB and qRT-PCR determined the key proteins and genes expression of TLR4, MyD88, TRAF-6 and NF-κB significantly increased while protein and gene expression of TRAM had no significant increase. Also, TNF-α level extremely decreased by adding inhibitors of TLR4 and MyD88 which confirmed ABSP could immunologically regulate RAW264.7 byTLR4-MyD88 dependent pathway. This study would provide theoretical basis for further study on ABSP and be helpful for development of beneficial functionally foods and exploitation of this resource.
Fan Xinyu,Zhang Ying,Li Xinyu,Ding Junhui,Huang Jiaolong,Lian Kai,Duan Peng,Hu Chunhui,Xu Junchang
In this study, the effects of Ginsenoside Rg1 (Rg1), the primary bioactive constituent of Panax ginseng roots, on glucocorticoid-induced osteoporosis (GIOP) were examined using a zebrafish model, with a focus on elucidating its underlying mechanisms. Our findings demonstrated that Rg1 treatment inhibited osteoporosis induced by methylprednisolone (PN), as evidenced by increased mineralisation area and integrated optical density in the spine and skull of zebrafish larvae. Rg1 reduced the expression of bglap (an osteogenic marker gene) and increased the expression of traf (an osteoclast marker gene) compared with the PN group. Behavioural analysis revealed that Rg1 alleviated PN-induced hypoactivity, resulting in enhanced motion speed. Furthermore, transcriptome analysis identified 383 genes reversed by Rg1 treatment, with significant enrichment in skeletal system development. KEGG analysis indicated that Rg1 influenced several signalling pathways primarily involved in retinol, fat, protein and lipid metabolism. Several genes related to skeletal system development and retinol metabolism were validated by qRT-PCR. In summary, this study provides scientific evidence for the potential mechanisms of Rg1 in the therapeutic intervention of GIOP, highlighting its promise as a potential pharmacological agent for the prevention and treatment of osteoporosis.
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