Adiponectin promotes human jaw bone marrow mesenchymal stem cell chemotaxis via CXCL1 and CXCL8

脂联素通过 CXCL1 和 CXCL8 促进人类颌骨骨髓间充质干细胞趋化

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作者:Yinfei Pu, Mengke Wang, Yingying Hong, Yuwei Wu, Zhihui Tang

Abstract

Adiponectin (APN) is known to promote the osteogenic differentiation of human jaw bone marrow mesenchymal stem cells (h-JBMMSCs). However, the underlying mechanism has not been fully elucidated. Previously, we showed that APN could promote h-JBMMSC osteogenesis via APPL1-p38 by up-regulating osteogenesis-related genes. Here, we aimed to determine whether APN could promote h-JBMMSC chemotaxis through CXCL1/CXCL8. The CCK-8, wound healing and transwell assays were used to evaluate the proliferation, migration and chemotaxis of h-JBMMSCs with or without APN treatment. Chemotaxis-related genes were screened using RNA-seq, and the results were validated using real-time PCR and ELISA. We also performed Western blot using the AMPK inhibitor, WZ4003, and the p38 MAPK inhibitor, SB203580, to identify the signalling pathway involved. We found that APN could promote h-JBMMSC chemotaxis in the co-culture transwell system. CXCL1 and CXCL8 were screened and confirmed as the up-regulated target genes. The APN-induced CXCL1/8 up-regulation to promote chemotaxis could be blocked by CXCR2 inhibitor SB225002. Western blot revealed that the phosphorylation of AMPK and p38 MAPK increased in a time-dependent manner with APN treatment. Additionally, WZ4003 and SB203580 could suppress the APN-induced overexpression of CXCL1 and CXCL8. The results of the transwell chemotaxis assay also supported the above results. Our data suggest that APN can promote h-JBMMSC chemotaxis by up-regulating CXCL1 and CXCL8.

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