M2 Macrophages regulate cementogenic differentiation of human periodontal ligament stem cells by modu-lating oxidant-antioxidant system and mitophagy
10.3969/j.issn.1001-3733.2024.02.003
- VernacularTitle:M2型巨噬细胞通过调控氧化-抗氧化体系和线粒体自噬影响人牙周膜干细胞的成牙骨质分化潜能
- Author:
Dian GAN
1
;
Faming CHEN
;
Xuan LI
Author Information
1. 710032 西安,口颌系统重建与再生全国重点实验室,国家口腔疾病临床医学研究中心,陕西省口腔疾病国际联合研究中心,空军军医大学第三附属医院牙周病科
- Keywords:
Cementoblastic differentiation;
Macrophage polarization;
Periodontal ligament stem cells;
Mitophagy
- From:
Journal of Practical Stomatology
2024;40(2):164-172
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the effects of macrophage(Mφ)polarization on the cementogenic differentiation of human perio-dontal ligament stem cells(hPDLSCs)and the underlying mechanism.Methods:Human monocytic THP-1 cells were induced to M0,M1 and M2 Mφ subsets,then RPM1 1640 medium or supernatants of different Mφ phenotypes were mixed with an equal volume of ce-mentoblastic induction medium to generate conditioned mediums(CMs),and termed as CM-Control,CM-M0,CM-M1 and CM-M2,respectively.hPDLSCs were cultured with different CMs,and the hPDLSCs sheets were then wrapped around treated dentin matrix(TDM)to generate cell sheet/dentin complexes.The complexes were subcutaneously implanted into nude mice.The cementum-like tissue formation was evaluated by HE staining,immunofluorescent staining(IMF)and qRT-PCR were used to detect the expression level of cementogenic differentiation-related markers bone sialoprotein(BSP),cementum attachment protein(CAP)and cementum pro-tein-1(CEMP-1),oxidant-antioxidant system-related markers superoxide dismutase 1(SOD1)and nuclear factor erythroid 2-related factor 2(NRF2),mitophagy-related markers PTEN induced putative kinase 1(PINK1)and microtubule asso ciated proteins 1A/1B light chain 3(LC3).Results:In vivo,CM-M2-treated hPDLSCs(CM-M2)group formed more cementum-like tissues and expressed higher protein levels of CAP,CEMP-1,SOD1,PINK1 and LC3 than that in other groups.In vitro tests showed that,compared with CM-Control group,hPDLSCs incubated with CM-M2 increased the levels of BSP(P<0.01),CAP(P<0.001),CEMP-1(P<0.01)and SOD1(P<0.05),while no statistically significant difference was detected for NRF2(P>0.05),and increasedthe expression of PINK1(P<0.05).Conclusion:M2 Mφ regulate the cementogenic differentiation of hPDLSCs possibly via modulating oxidant-antioxidant system and mitophagy.