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Dicalcium silicate-induced mitochondrial dysfunction and autophagy-mediated macrophagic inflammation promotes osteogenic differentiation of BMSCs

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Regenerative Biomaterials 2022年第1期9卷 93-106页

作者： Qianting Luo Xingyang Li Wenchao Zhong Wei Cao Mingjing Zhu Antong Wu Wanyi Chen Zhitong Ye Qiao Han duraipandy natarajan Janak L.Pathak Qingbin Zhang Department of Temporomandibular Joint Affiliated Stomatology Hospital of Guangzhou Medical UniversityGuangdong Engineering Research Center of Oral Restoration and ReconstructionGuangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative MedicineGuangzhou 510182China Jiangmen Central Hospital Affiliated Jiangmen Hospital of Sun Yat-sen UniversityJiangmen 529030China Department of Oral Cell Biology Academic Centre of Dentistry Amsterdam(ACTA)Vrije Universiteit Amsterdam and University of AmsterdamAmsterdam 1081LAThe Netherlands Affiliated Stomatology Hospital of Guangzhou Medical University Guangdong Engineering Research Center of Oral Restoration and ReconstructionGuangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative MedicineGuangzhou 510182China

Dicalcium silicate(Ca_(2)SiO_(4),C_(2)S)has osteogenic potential but induces macrophagic *** function plays a vital role in macrophage polarization and macrophagic *** mitochondrial function of C_(2)S-treated macrophages is still *** study hypothesized:(i)the C_(2)S modulates mitochondrial function and autophagy in macrophages to regulate macro-phagic inflammation,and(ii)C_(2)S-induced macrophagic inflammation regulates *** used RAW264.7 cells as a model of *** C_(2)S(75–150μg/ml)extract was used to analyze the macrophagic mitochondrial function and macrophagemediated effect on osteogenic differentiation of mouse bone marrow-derived mesenchymal stem cells(BMSCs).The results showed that C_(2)S extract(150μg/ml)induced TNF-α,IL-1βand IL-6 production in macrophages.C_(2)S extract(150μg/ml)enhanced reactive oxygen species level and intracellular calcium level but reduced mitochondrial membrane potential and ATP *** images showed reduced mitochondrial abundance and altered the mitochondrial morphology in C_(2)S(150μg/ml)-treated *** level expression of PINK1,Parkin,Beclin1 and LC3 was upregulated but TOMM20 was *** sequencing and KEGG analysis showed that C_(2)S-induced differentially expressed mRNAs in macrophages were mainly distributed in the essential signaling pathways involved in mitochondrial function and *** conditioned medium from C_(2)S-treated macrophage robustly promoted osteogenic differentiation in *** conclusion,our results indicate mitochondrial dysfunction and autophagy as the possible mechanism of C_(2)S-induced macrophagic *** promotion of osteogenic differentiation of BMSCs by the C_(2)S-induced macrophagic inflammation suggests the potential application of C_(2)S in developing immunomodulatory bone grafts.

关键词： dicalcium silicate macrophagic inflammation mitochondrial function autophagy osteogenesis

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