M2 Macrophages Enhance the Cementoblastic Differentiation of Periodontal Ligament Stem Cells via the Akt and JNK Pathways. (24th August 2019)

• Record Type: Journal Article
• Authors: Li, Xuan; He, Xiao-Tao; Kong, De-Qin; Xu, Xin-Yue; Wu, Rui-Xin; Sun, Li-Juan; Tian, Bei-Min; Chen, Fa-Ming
• Is Part Of: Stem cells. Volume 37:Number 12(2019)
• Page Start: 1567
• Page End: 1580
• Publication Date: 2019-08-24
• Subjects: Macrophage polarization -- Cementoblastic differentiation -- Akt pathway -- JNK pathway -- Cyto-/chemokines; Cloning -- Periodicals; Clone cells -- Periodicals; Stem cells -- Periodicals; Cell Differentiation -- Periodicals; Cell Division -- Periodicals; Clone Cells -- Periodicals; Hematopoietic Stem Cells -- Periodicals; Stem Cells -- Periodicals; 571.84
• DOI: 10.1002/stem.3076
• Languages: English
• ISSNs: 1066-5099

Abstract

Abstract: Although macrophage (Mφ) polarization has been demonstrated to play crucial roles in cellular osteogenesis across the cascade of events in periodontal regeneration, how polarized Mφ phenotypes influence the cementoblastic differentiation of periodontal ligament stem cells (PDLSCs) remains unknown. In the present study, human monocyte leukemic cells (THP-1) were induced into M0, M1, and M2 subsets, and the influences of these polarized Mφs on the cementoblastic differentiation of PDLSCs were assessed in both conditioned medium-based and Transwell-based coculture systems. Furthermore, the potential pathways and cyto-/chemokines involved in Mφ-mediated cementoblastic differentiation were screened and identified. In both systems, M2 subsets increased cementoblastic differentiation-related gene/protein expression levels in cocultured PDLSCs, induced more PDLSCs to differentiate into polygonal and square cells, and enhanced alkaline phosphatase activity in PDLSCs. Furthermore, Akt and c-Jun N-terminal Kinase (JNK) signaling was identified as a potential pathway involved in M2 Mφ-enhanced PDLSC cementoblastic differentiation, and cyto-/chemokines (interleukin (IL)-10 and vascular endothelial growth factor [VEGF]) secreted by M2 Mφs were found to be key players that promoted cell cementoblastic differentiation by activating Akt signaling. Our data indicate for the first time that Mφs are key modulators during PDLSC cementoblastic differentiation and are hence very important for the regeneration of multiple periodontal tissues, including the cementum. Although the Akt and JNK pathways are involved in M2 Mφ-enhanced cementoblastic differentiation, only the Akt pathway can be activated via a cyto-/chemokine-associated mechanism, suggesting that players other than cyto-/chemokines also participate in the M2-mediated cementoblastic differentiation of PDLSCs. Stem Cells 2019;37:1567–1580 : Abstract : Both the Akt and JNK axes are involved in the M2 macrophage-enhanced cementoblastic differentiation of periodontal ligament stem cells, but only the Akt pathway can be activated via a cyto-/chemokine-associated mechanism.