Toll-like receptor 4 deficiency affects the balance of osteoclastogenesis and osteoblastogenesis in periodontitis
Lu Pan, He She, Yong Hu, Laikui Liu, Hongyan Wang, Lifang Zhu
Abstract
• TLR4 deficiency could reduce the bone loss in periodontitis. • Periodontal soft tissue injury in periodontitis did not depend on TLR4. • Knocking out TLR4 decreased osteoclastogenesis by suppressing TRACP, CTSK and NFATc1. • TLR4/AP1 axis dysregulation promoted osteogenesis and thus reduced bone destruction. Toll-like receptor 4 (TLR4) acts as a double-edged sword in the occurrence and development of periodontitis. While the activation of TLR4 in macrophages aids in clearing local pathogens, it can also disrupt innate immune responses, upsetting microecological balance and accelerating the destruction of periodontal bone tissues. To date, the effects of TLR4 on osteogenesis and osteoclastogenesis in periodontitis have not been comprehensively studied. In this study, we investigated the development of periodontitis in the Tlr4 −/− mice by ligating their second molars with silk threads. Compared to wild-type (WT) mice, Tlr4 −/− mice demonstrated increased resistance to periodontitis-associated bone destruction, as evidenced by decreased bone resorption and enhanced bone regeneration. Mechanistically, the deletion of Tlr4 not only inhibited osteoclast formation by reducing the expression of NFATc1, CTSK and TRAP, but also enhanced osteogenic abilities through increased expression of OCN, OPN and RUNX2. In conclusion, TLR4 tips the balance of osteoclastogenesis and osteogenesis, thereby promoting periodontal bone destruction in periodontitis.