IL-7 suppresses osteogenic differentiation of periodontal ligament stem cells through inactivation of mitogen-activated protein kinase pathway

Abstract

ABSTRACT. Periodontal ligament stem cells (PDLSCs) are tissue-specific mesenchymal stem cells (MSCs), having an important role in regenerative therapy for teeth loss. Interleukin-7 (IL-7) is a key cytokine produced by stromal cells including MSCs, and exhibits specific roles for B and T cell development and osteoblasts differentiation of multiple myeloma. However, the effect of IL-7 on osteogenic differentiation of PDLSCs remains unclear. Therefore, in the present study we determined whether IL-7 affects the proliferation and osteogenic differentiation of PDLSCs in vitro and explored the associated signaling pathways for IL-7-mediated cell differentiation. The results demonstrated that the isolated human PDLSCs possessed MSCs features, highly expressing CD90, CD44, CD105, CD29 and CD73, and almost did not expressed CD34, CD45, CD11b, CD14 and CD117. IL-7 could not significantly affect the proliferation of PDLSCs, but it decreased their osteogenic differentiation and inhibited alkaline phosphatase (ALP) activity. The results of quantitative reverse transcriptionpolymerase chain reaction (qRT-PCR) and Western blotting exhibited that the expression levels of Runx-2, SP7 and osteocalcin (OCN) were significantly reduced by IL-7. Further studies indicated that IL-7 did not significantly change JNK, ERK1/2 and p38 protein production, but markedly suppressed their phosphorylation levels. These data suggest that IL-7 inhibits the osteogenic differentiation of PDLSCs probably via inactivation of mitogen-activated protein kinase (MAPK) signaling pathway.

CB1 enhanced the osteo/dentinogenic differentiation ability of periodontal ligament stem cells via p38 MAPK and JNK in an inflammatory environment

“…Several studies have confirmed that p38 MAPK and JNK are positive regulators of osteogenic differentiation. 56,57 For example, BMP2 induces osteoblastic cell differentiation via activation of the p38 MAPK and JNK pathways. 58 Periostin promotes the osteogenic differentiation potential of PDLSCs through the JNK pathway under inflammatory conditions.…”

TET2 Loss Dysregulates the Behavior of Bone Marrow Mesenchymal Stromal Cells and Accelerates Tet2-Driven Myeloid Malignancy Progression

“…We confirmed 11 genes that are related to osteoblast differentiation and bone development by qPCR. The upregulated genes ( Trp63 , Fbn2 , Sfrp2 , Adamts12, and Eya1 ) are all positive regulators of osteoblast differentiation ( Cho et al., 2008 , Ji et al., 2016 , Nistala et al., 2010 , Sworder et al., 2015 , Yang et al., 1999 ), and the downregulated genes ( Hes1 , Wnt9a , Syk, Comp, IL-7, and Nox4 ) are negatively impacted in osteoblast differentiation ( Guo et al., 2014 , Jian et al., 2016 , Mandal et al., 2011 , Yoshida et al., 2011 , Zhang et al., 2009 , Zhou et al., 2009 ). These altered genes may cooperate to contribute the enhanced osteoblast differentiation potential in Tet2 −/− mice.…”

Regulation of Osteoblast Differentiation by Cytokine Networks

“…It has been reported that direct injection of IL-7 in mice inhibits bone formation [ 105 ]. In periodontal ligament stem cells, IL-7 suppresses osteoblastogenesis by downregulating osteoblastogenic markers, such as RUNX2, OSX, ALP, and OCN, through the inactivation of the MAPK pathway [ 106 ]. In multiple myeloma, IL-7 is implicated in inhibiting bone formation by suppressing RUNX2 activity [ 107 ].…”