NLRP12 Alleviated Periodontal Destruction via Suppressing Nuclear Factor Kappa-B Signalling Pathway

Periodontal ligament stem cells (PDLSCs) have been shown to demonstrate robust tissue regeneration capabilities. NACHT, leucine-rich repeat and PYD-containing 12 (NLRP12) could exerts negative inflammatory regulatory role in various pathological contexts. The effects of NLRP12 on the inflammatory responses and osteogenesis of PDLSCs under inflammatory microenvironment and underlying mechanisms remain unknown.

PDLSCs were isolated, cultured, and characterized, and the expression level of NLRP12 was analysed following lipopolysaccharide (LPS) treatment. Then, NLRP12 was overexpressed in PDLSCs via lentivirus transfection. Inflammatory factors were detected by quantitative real-time polymerase chain reaction, osteogenic markers were quantified using quantitative real-time polymerase chain reaction, Western blot, and the capability of osteogenesis was assessed through alkaline phosphatase staining and alizarin red staining. The underlying signalling pathways were examined by Western blot analysis and agonist treatment. Moreover, rat periodontitis models established by ligature method were used to evaluate the regulatory effects of NLRP12 on PDLSC-mediated anti-inflammation and periodontal regeneration in vivo.

PDLSCs exhibited mesenchymal stem cell characteristics with multilineage differentiation. NLRP12 was downregulated in LPS-treated PDLSCs. LPS upregulated inflammatory factor expression while downregulating anti-inflammatory factors and suppressing PDLSCs' osteogenic differentiation, which were reversed by NLRP12 overexpression. Mechanistically, nuclear factor kappa-B signalling pathway participated in these processes. Furthermore, microscopic computed tomography scanning, histological analysis, and immunohistochemical staining revealed that NLRP12 ameliorated inflammation and enhanced periodontal regeneration in periodontitis animal models.

NLRP12 suppressed inflammatory responses while enhancing osteogenic differentiation of PDLSCs via downregulating the activation of the nuclear factor kappa-B pathway, indicating that NLRP12 is a latent target for enhancing PDLSCs-based periodontal tissue regeneration.