Inhibition of PTGS1 promotes osteogenic differentiation of adipose-derived stem cells by suppressing NF-kB signaling

Abstract

Background Tissue inflammation is an important problem in the field of human adipose-derived stem cell (ASC)-based therapeutic bone regeneration. Many studies indicate that inflammatory cytokines are disadvantageous for osteogenic differentiation and bone formation. Therefore, overcoming inflammation would be greatly beneficial in promoting ASC-mediated bone regeneration. The present study aims to investigate the potential anti-inflammatory role of Prostaglandin G/H synthase 1 (PTGS1) during the osteogenic differentiation of ASCs. Methods We performed TNFα treatment to investigate the response of PTGS1 to inflammation. Loss- and gain-of-function experiments were applied to investigate the function of PTGS1 in the osteogenic differentiation of ASCs ex vivo and in vivo. Western blot and confocal analyses were used to determine the molecular mechanism of PTGS1-regulated osteogenic differentiation. Results Our work demonstrates that PTGS1 expression is significantly increased upon inflammatory cytokine treatment. Both ex vivo and in vivo studies indicate that PTGS1 is required for the osteogenic differentiation of ASCs. Mechanistically, we show that PTGS1 regulates osteogenesis of ASCs via modulating the NF-κB signaling pathway. Conclusions Collectively, this work confirms that the PTGS1-NF-κB signaling pathway is a novel molecular target for ASC-mediated regenerative medicine. Electronic supplementary material The online version of this article (10.1186/s13287-019-1167-3) contains supplementary material, which is available to authorized users.

Human Cytomegalovirus Long Non-coding RNA1.2 Suppresses Extracellular Release of the Pro-inflammatory Cytokine IL-6 by Blocking NF-κB Activation

“…Our transcriptomic analysis identified RNA1.2 as downregulating PIM1 (Nihira et al, 2010 ) and upregulate SEMA3A (Sumi et al, 2018 ), which have been reported to activate and suppress, respectively, NF-κB signaling in other cell types and contexts, and thus may contribute to RNA1.2 stimulated increase in IL-6 levels. However, the screen also identified RNA1.2 as downregulating six other potential inhibitors of NF-κB: RCAN1 (Chen et al, 2017 ), IFRD1(Micheli et al, 2011 ), HBEGF (Mehta and Besner, 2005 ), SDC1 (Zhang et al, 2016 ), TSC22D3 (Di Marco et al, 2007 ) and PTGS1 (Wang et al, 2019 ). Their modulation of NF-κB is likely to be contextual to cell type and biological process, and thus further work will be required to determine whether they influence NF-κB activity during infection.…”

Promoting Osteogenic Differentiation of Human Adipose-Derived Stem Cells by Altering the Expression of Exosomal miRNA

“…Understanding the precise molecular mechanisms of osteogenesis is of immense importance for promoting the osteogenic efficacy and clinical application of stem cells in bone regeneration. To date, most research has focused on the study of epigenetic and transcriptional factors involving stem cells themselves [45–47], whereas few studies have focused on the effects of exosome “cargo” on the osteogenic differentiation of stem cells. It has been noted that exosomes can regulate corresponding biological processes by affecting related pathways in receptor cells.…”

ZBTB46, SPDEF, and ETV6: Novel Potential Biomarkers and Therapeutic Targets in Castration-Resistant Prostate Cancer

“…Chen et al showed that in ADT-treated PCa, ZBTB46 levels were enhanced by loss of the expression of the SAM pointed domain-containing ETS transcriptional factor ( SPDEF ), which is believed to act as a tumor suppressor gene and to be regulated by AR signaling [118]. A low level of SPDEF leads to an increase in the expression of ZBTB46 , thus facilitating an abundance of prostaglandin endoperoxide synthase 1 ( PTGS1 ), which was reported to participate in inflammation, arthritis, and cancer pathophysiology [119,120,121,122]. Those studies demonstrated that ZBTB46 acts as a transcriptional coactivator and induces PTGS1 expression.…”