Remodeling periodontal osteoimmune microenvironment through MAPK/NFκB phosphorylation pathway of macrophage via intelligent ROS scavenging

Abstract

Periodontitis is an in ammatory disorder which leads to the defect of tooth-supporting tissue, especially in alveolar bone. During this process, the polarization behavior of macrophages affects immune in ammation and bone regeneration in which reactive oxygen species(ROS) play an essential role. ROS level should be regulated to the physiological level to protect stem cells from the in ammatory immune microenvironment. Our previous study constructed a ROS-responsive nanoplatform (Pssl-NAC), which possessed ROS-responsive antioxidative effect and could be potentially applied in periodontitis. However, the connection among bone regeneration, in ammation and oxidative stress remained in osteoimmune regulation is not clear. To further investigate the mechanism of the way how Pssl-NAC works in the treatment of periodontitis would be meaningful. Here, we investigated the effect of PssL-NAC in the regulation of the osteoimmune microenvironment through macrophage polarization. Results show PssL-NAC regulated the macrophage polarization direction in an in ammatory environment by maintaining an appropriate level of intracellular ROS, in which the MAPK/NFκB phosphorylation pathway is particularly important. In the macrophage-hPDLSCs co-culture system, PssL-NAC treatment signi cantly enhanced the osteogenic differentiation of hPDLSCs. In vivo experiment further con rmed the M2 macrophages increased in the periodontal tissue of rats, and the expression of iNOS and p65 decreased after PssL-NAC treatment. In conclusion, PssL-NAC regulates the osteoimmune microenvironment and protects stem cells from oxidative stress injury for bone regeneration, which provides a strategy for the treatment of periodontitis.

The role of N-acetylcysteine in osteogenic microenvironment for bone tissue engineering

“…The change of polarization can modulate the production of proinflammatory and anti-inflammatory cytokines by macrophages, thus regulating the bone-immune microenvironment and preventing alveolar bone loss ( Pajarinen et al, 2019 ; Zhang B. et al, 2021 ). Conversely, other research reveals that sustained low ROS levels may enhance M2 macrophage polarization without significantly affecting M1 macrophages ( Qiu et al, 2023 ). Further investigation is required to clarify the role of NAC in macrophage polarization regulation.…”

The Genetic Aspects of Periodontitis Pathogenesis and the Regenerative Properties of Stem Cells

“…The generation of reactive oxygen species (ROS) is correlated with both physiological and pathological properties, as these molecules can kill microorganisms as well as host cells [167]. Scavenging ROS using antioxidant agents or platforms could enhance the osteogenic features of PDLSCs [168,169]. For instance, the overexpression of superoxide dismutase 2 in PDLSCs stimulated the expression of osteogenic markers.…”