UCHL1 Exacerbates Periodontitis by Coordinating Mitochondrial Dysfunction and Endoplasmic Reticulum Stress in...

Area of Science:

• Immunology
• Periodontal Medicine
• Biomaterials Science

Background:

• Macrophages are key players in periodontitis progression and regeneration.
• Ubiquitin carboxyl-terminal hydrolase L1 (UCHL1) is involved in inflammation, but its role in periodontitis-associated macrophages is unclear.

Purpose of the Study:

• To investigate the role of UCHL1 in macrophage immune response during periodontitis.
• To explore UCHL1 inhibition as a therapeutic strategy for periodontitis management.

Main Methods:

• Used ligature-induced periodontitis mice and P.g LPS to study UCHL1 expression.
• Employed lentivirus and inhibitors to determine UCHL1's function in macrophages.
• Assessed macrophage mitochondrial function and ER stress.
• Developed and tested UCHL1 inhibitor-loaded hydrogels for periodontitis treatment.

Main Results:

• UCHL1 expression was upregulated in periodontitis-associated macrophages.
• UCHL1 inhibition decreased pro-inflammatory cytokines (TNF-α, IL-6, IL-1β).
• Inhibition improved osteogenesis and MC3T3-E1 cell migration.
• UCHL1 inhibition mitigated LPS-induced mitochondrial damage and ER stress.
• Hydrogels demonstrated anti-inflammatory and bone-promoting effects in vitro and in vivo, alleviating inflammation and enhancing bone regeneration.

Conclusions:

• UCHL1 acts as a negative regulator in periodontitis.
• Inhibiting UCHL1 can improve the periodontal inflammatory environment.
• Targeting UCHL1 is a promising approach for promoting alveolar bone regeneration in periodontitis.