International dental journal · 2025
FBXO5 alleviates apical periodontitis by facilitating TP53 protein degradation.
СтатьяНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
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Ошибки и ограничения
История · было → стало
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Zhang Ruihan, Xiong Menglin, Li Boqi, Sheng Li, Zhang Bei, Wang Mengqi, Liu Jia
Аннотация
BACKGROUND: Apical periodontitis (AP) is a common inflammatory disease that irreversibly damages apical papilla tissue and hinders dental regeneration. The molecular mechanisms underlying F-box protein 5 (FBXO5)- and tumor protein p53 (TP53)-mediated regulation of osteogenic differentiation in human stem cells from the apical papilla (hSCAPs) remain to be fully elucidated, particularly in the context of AP pathogenesis.
METHODS: Differentially expressed genes in the AP tissues from AP patients and normal controls were identified through bioinformatics analysis. The hSCAPs were isolated from the third molars of healthy human individuals. Alkaline phosphatase (ALP) staining and ALP activity assay, along with Alizarin Red S (ARS) staining, were performed to assess osteogenic differentiation. Stem cell characteristics were identified by flow cytometry. The mRNA and protein expression levels were evaluated by RT-qPCR and Western blotting, respectively. Cell viability and proliferation were assessed using cell counting kit-8 (CCK-8) and 5-ethynyl-2'-deoxyuridine (EdU) assays. The interaction between FBXO5 and TP53 was analyzed by co-immunoprecipitation (Co-IP), cycloheximide (CHX) chase and protein ubiquitination assays.
RESULTS: FBXO5 expression was downregulated in AP tissues. FBXO5 knockdown reduced hSCAPs proliferation and impaired their osteogenic differentiation. Mechanistically, FBXO5 facilitated TP53 ubiquitination-mediated degradation, enhanced hSCAP proliferation by downregulating TP53, and promoted osteogenic differentiation by negatively regulating TP53, showing its key role in maintaining stem cell function during AP progression.
CONCLUSION: FBXO5 promoted TP53 degradation to regulate osteogenic differentiation in hSCAPs, which contributed to AP progression. Targeting FBXO5 may provide a potential therapeutic strategy for AP.
METHODS: Differentially expressed genes in the AP tissues from AP patients and normal controls were identified through bioinformatics analysis. The hSCAPs were isolated from the third molars of healthy human individuals. Alkaline phosphatase (ALP) staining and ALP activity assay, along with Alizarin Red S (ARS) staining, were performed to assess osteogenic differentiation. Stem cell characteristics were identified by flow cytometry. The mRNA and protein expression levels were evaluated by RT-qPCR and Western blotting, respectively. Cell viability and proliferation were assessed using cell counting kit-8 (CCK-8) and 5-ethynyl-2'-deoxyuridine (EdU) assays. The interaction between FBXO5 and TP53 was analyzed by co-immunoprecipitation (Co-IP), cycloheximide (CHX) chase and protein ubiquitination assays.
RESULTS: FBXO5 expression was downregulated in AP tissues. FBXO5 knockdown reduced hSCAPs proliferation and impaired their osteogenic differentiation. Mechanistically, FBXO5 facilitated TP53 ubiquitination-mediated degradation, enhanced hSCAP proliferation by downregulating TP53, and promoted osteogenic differentiation by negatively regulating TP53, showing its key role in maintaining stem cell function during AP progression.
CONCLUSION: FBXO5 promoted TP53 degradation to regulate osteogenic differentiation in hSCAPs, which contributed to AP progression. Targeting FBXO5 may provide a potential therapeutic strategy for AP.