NLRP3-mediated periodontal ligament cell pyroptosis promotes root resorption.
J Clin Periodontol
; 51(4): 474-486, 2024 04.
Article
en En
| MEDLINE
| ID: mdl-38164052
ABSTRACT
AIM:
To investigate the mechanisms by which periodontal ligament cells (PDLCs) convert biomechanical stimulation into inflammatory microenvironment inducing root resorption (RR). MATERIALS ANDMETHODS:
RNA sequencing was employed to explore mechanisms in force-inflammatory signal transduction. Then resorption volume, odontoclastic activity, PDLC pyroptotic ratio and NOD-like receptor protein 3 (NLRP3)-mediated pyroptosis pathway activation were analysed under force and pyroptosis inhibition. Further osteoclast formation, macrophage number and transwell polarization demonstrated the effects of PDLC pyroptosis on osteoclastogenesis and M1 polarization.RESULTS:
RNA sequencing revealed that NLRP3-mediated PDLC pyroptosis induced by Toll-like receptor 4 (TLR4)/nuclear factor kappa B (NFκB)/NLRP3 pathway may be involved in mechano-inflammatory signal transduction. PDLC pyroptosis under force and the expression of NLRP3-mediated pyroptosis pathway in force-enhanced PDLCs were significantly increased, both in vivo and in vitro. MCC950 administration was sufficient to reduce PDLC pyroptosis and alleviate RR, odontoclast formation and M1 polarization in vivo. Further in vitro exploration showed that MCC950 treatment reduced PDLC force-promoted pyroptosis and blocked NLRP3-mediated pyroptosis pathway. Moreover, by treating THP-1 with force-pretreated PDLCs or supernatants, NLRP3-mediated PDLC pyroptotic released products induced osteoclast formation and M1 polarization.CONCLUSIONS:
NLRP3-mediated PDLC pyroptosis promotes RR. PDLCs transmit excessive force into inflammation signals through TLR4/NFκB/NLRP3 pathway, inducing PDLC pyroptosis, which directly promotes odontoclast formation and subsequent RR or promotes M1 polarization to indirectly trigger odontoclastogenesis and RR.Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Resorción Radicular
/
Proteínas NLR
Límite:
Humans
Idioma:
En
Revista:
J Clin Periodontol
Año:
2024
Tipo del documento:
Article
País de afiliación:
China