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Pyroptotic macrophages induce disruption of glutamate metabolism in periodontal ligament stem cells contributing to their compromised osteogenic potential.
Sun, Li-Juan; Qu, Hong-Lei; He, Xiao-Tao; Tian, Bei-Min; Wu, Rui-Xin; Yin, Yuan; Zou, Jie-Kang; Sun, Hai-Hua; Li, Xuan; Chen, Fa-Ming.
Afiliación
  • Sun LJ; State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, Department of Periodontology, School of Stomatology, The Fourth Military Medical University, Xi'an, Ch
  • Qu HL; State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, Department of Periodontology, School of Stomatology, The Fourth Military Medical University, Xi'an, Ch
  • He XT; State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, Department of Periodontology, School of Stomatology, The Fourth Military Medical University, Xi'an, Ch
  • Tian BM; State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, Department of Periodontology, School of Stomatology, The Fourth Military Medical University, Xi'an, Ch
  • Wu RX; State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, Department of Periodontology, School of Stomatology, The Fourth Military Medical University, Xi'an, Ch
  • Yin Y; State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, Department of Periodontology, School of Stomatology, The Fourth Military Medical University, Xi'an, Ch
  • Zou JK; State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, Department of Periodontology, School of Stomatology, The Fourth Military Medical University, Xi'an, Ch
  • Sun HH; State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, Department of General Dentistry and Emergency, School of Stomatology, The Fourth Military Medical Univ
  • Li X; State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, Department of Periodontology, School of Stomatology, The Fourth Military Medical University, Xi'an, Ch
  • Chen FM; State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, Department of Periodontology, School of Stomatology, The Fourth Military Medical University, Xi'an, Ch
Cell Prolif ; 57(10): e13663, 2024 Oct.
Article en En | MEDLINE | ID: mdl-38803043
ABSTRACT
Macrophage pyroptosis is of key importance to host defence against pathogen infections and may participate in the progression and recovery of periodontitis. However, the role of pyroptotic macrophages in regulating periodontal ligament stem cells (PDLSCs), the main cell source for periodontium renewal, remains unclear. First, we found that macrophage pyroptosis were enriched in gingiva tissues from periodontitis patients compared with those of healthy people through immunofluorescence. Then the effects of pyroptotic macrophages on the PDLSC osteogenic differentiation were investigated in a conditioned medium (CM)-based coculture system in vitro. CM derived from pyroptotic macrophages inhibited the osteogenic differentiation-related gene and protein levels, ALP activity and mineralized nodule formation of PDLSCs. The osteogenic inhibition of CM was alleviated when pyroptosis was inhibited by VX765. Further, untargeted metabolomics showed that glutamate limitation may be the underlying mechanism. However, exogenous glutamate supplementation aggravated the CM-inhibited osteogenic differentiation of PDLSCs. Moreover, CM increased extracellular glutamate and decreased intracellular glutamate levels of PDLSCs, and enhanced the gene and protein expression levels of system xc - (a cystine/glutamate antiporter). After adding cystine to CM-based incubation, the compromised osteogenic potency of PDLSCs was rescued. Our data suggest that macrophage pyroptosis is related to the inflammatory lesions of periodontitis. Either pharmacological inhibition of macrophage pyroptosis or nutritional supplements to PDLSCs, can rescue the compromised osteogenic potency caused by pyroptotic macrophages.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Osteogénesis / Ligamento Periodontal / Periodontitis / Células Madre / Diferenciación Celular / Ácido Glutámico / Piroptosis / Macrófagos Límite: Female / Humans / Male Idioma: En Revista: Cell Prolif Año: 2024 Tipo del documento: Article Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Osteogénesis / Ligamento Periodontal / Periodontitis / Células Madre / Diferenciación Celular / Ácido Glutámico / Piroptosis / Macrófagos Límite: Female / Humans / Male Idioma: En Revista: Cell Prolif Año: 2024 Tipo del documento: Article Pais de publicación: Reino Unido