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Targeting CTSS Rescues LPS-Induced Osteogenic Impairment in PDLSCs via Blocking NF-κB-Dependent Inflammatory
Dong Shen1, Lihua Qiu1, Jie Wang1
1Department of Stomatology, Yancheng Stomatological Hospital, Yancheng City, China.
Objective(S):
This study aimed to elucidate the role of Cathepsin S (CTSS) in periodontitis, focusing on its dual impact on inflammation and osteogenic differentiation of periodontal ligament stem cells (PDLSCs).
Materials And Methods:
Integrated bioinformatics analysis of GEO datasets was performed, followed by experimental validation using PDLSCs from healthy individuals and periodontitis patients. Functional assays included CTSS knockdown/overexpression, LPS stimulation, osteogenic differentiation assessment, and evaluation of NF-κB signaling and inflammatory cytokines.
Results:
Bioinformatics and experimental data consistently showed CTSS upregulation in periodontitis. CTSS knockdown enhanced osteogenic differentiation and mineralization while inhibiting LPS-induced NF-κB activation and pro-inflammatory cytokine expression (TNF-α, IL-1β, and IL-6); CTSS overexpression produced opposite effects.
Conclusion(S):
CTSS drives inflammation and suppresses PDLSC regenerative capacity via NF-κB activation, positioning it as a promising therapeutic target for periodontal tissue regeneration.

