GalNAc-Conjugated siRNA Targeting Complement C3 Inhibits Osteoclast Activation in Periodontitis.

Autor: Chen Y; Laboratory of Tissue Regeneration and Immunology and Department of Periodontics, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, School of Stomatology, Capital Medical University, Beijing, People's Republic of China.; Immunology Research Center for Oral and Systemic Health, Beijing Friendship Hospital, Capital Medical University, Beijing, People's Republic of China., Liu Y; Laboratory of Tissue Regeneration and Immunology and Department of Periodontics, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, School of Stomatology, Capital Medical University, Beijing, People's Republic of China.; Immunology Research Center for Oral and Systemic Health, Beijing Friendship Hospital, Capital Medical University, Beijing, People's Republic of China., Fu Z; Suzhou Ribo Life Science co. Ltd., Jiangsu, China., Xu J; Laboratory of Tissue Regeneration and Immunology and Department of Periodontics, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, School of Stomatology, Capital Medical University, Beijing, People's Republic of China.; Immunology Research Center for Oral and Systemic Health, Beijing Friendship Hospital, Capital Medical University, Beijing, People's Republic of China., Guo L; Department of Orthodontics, School of Stomatology, Capital Medical University, Beijing, People's Republic of China., Cao H; Suzhou Ribo Life Science co. Ltd., Jiangsu, China., Gan L; Suzhou Ribo Life Science co. Ltd., Jiangsu, China.; Ribocure Pharmaceuticals AB, Gothenburg, Sweden., Gao S; Suzhou Ribo Life Science co. Ltd., Jiangsu, China., Liu Y; Laboratory of Tissue Regeneration and Immunology and Department of Periodontics, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, School of Stomatology, Capital Medical University, Beijing, People's Republic of China.; Immunology Research Center for Oral and Systemic Health, Beijing Friendship Hospital, Capital Medical University, Beijing, People's Republic of China.
Jazyk: angličtina
Zdroj: Oral diseases [Oral Dis] 2024 Oct 29. Date of Electronic Publication: 2024 Oct 29.
DOI: 10.1111/odi.15170
Abstrakt: Objective: The complement cascade plays an important role in the inflammation amplification and tissue destruction of periodontitis. Importantly, complement C3 was proved to be the central element of complement cascade. Thus, targeting inhibition of C3 has become one of the focuses of treatment method development and exploration.
Methods: The siRNAs targeting C3 were designed and screened for in vitro potency. The selected siRNA was conjugated to GalNAc (GalNAc-C3 siRNA) for liver-specific delivery. The mouse model of periodontitis was established by silk ligation. Stereomicroscopy, Micro-CT, histological and histochemical assessment, and immunofluorescence staining were performed to evaluate the level of bone destructive and osteoclast activity. The influence of GalNAc-C3 siRNA on inflammatory reactions was determined by qRT-PCR, ELISA, and flow cytometry.
Results: GalNAc-C3 siRNA showed great in vivo potency and durability to silence hepatic C3 mRNA expression. GalNAc-C3 siRNA treatment could effectively inhibit the production of inflammatory cytokines (IL-17A, TNF-α, IL-6, and IFN-γ) and restrain Th17 differentiation. Importantly, the expression of RANKL and differentiation of osteoclast were inhibited by GalNAc-C3 siRNA.
Conclusion: GalNAc-C3 siRNA could efficiently play a role in bone protection by inhibiting inflammatory responses and osteoclast activities. This therapeutic siRNA may become an effective treatment strategy for periodontitis.
(© 2024 John Wiley & Sons Ltd.)
Databáze: MEDLINE
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