COMP‐Ang1 promotes chondrogenic and osteogenic differentiation of multipotent mesenchymal stem cells through the Ang1/Tie2 signaling pathway

Abstract

Mesenchymal stem cells (MSCs) are pleiotrophic cells that differentiate to chondrocytes, osteoblasts, or adipocytes, as a result of crosstalk by specific signaling pathways including MAPK pathway. Recently cartilage oligomeric matrix protein angiopoietin1 (COMP-Ang1), an Ang1 variant which is more potent than native Ang1 in phosphorylating Tie2 receptor was developed. The Ang1/Tie2 signaling system not only plays a pivotal role in vessel growth, remodeling, and maturation, but also protective and recruit effect on MSCs. Thus, the aim of the present study was to investigate the differentiate effect of Ang1/Tie2 signaling on MSCs in the presence of chondrogenic, osteogenic and adipogenic induction medium, and to determine the possible mechanisms. Our results clearly demonstrated that MSCs cultured in each induction medium with COMP-Ang1 revealed strongly chondrogenic and osteogenic morphological change (3.5- and 2-fold, respectively) as well as up-regulate each gene, except for adipogenic differentiation. Accordingly, we found that phosphorylation of Tie2 expression lead to phosphorylation of p38 and AKT and then accelerating each differentiation of MSCs to chondrocytes and osteoblasts. Therefore, our findings suggest that COMP-Ang1 present a portal to promote MSCs differentiation to chondrocytes and osteoblasts through Ang1/Tie2 signaling pathway and provide insights into novel therapies for bone diseases.

Macrophages Contribute to the Progression of Infantile Hemangioma by Regulating the Proliferation and Differentiation of Hemangioma Stem Cells

“…Consistent with a previous study in which PDGF promoted the proliferation and self-renewal, whereas suppressed the adipogenesis of mesenchymal stem cells (Gharibi et al, 2012), we showed that PDGF suppressed the adipogenesis of HemSCs induced by polarized macrophages ( Supplementary Figure 8 online). Furthermore, inflammatory cytokines participate in the differentiation of stem/progenitor cells (Al-Lamki et al, 2013;Kim et al, 2013;Ventayol et al, 2014), including adipogenesis (Floyd et al, 2007;van Asseldonk et al, 2010). In the present study, TNF-α antibody can partially rescue the suppressed adipogenesis of HemSCs induced by M1polarized macrophages ( Supplementary Figure 8 online).…”

Space microgravity drives transdifferentiation of human bone marrow‐derived mesenchymal stem cells from osteogenesis to adipogenesis

“…These genes reportedly play an important role in the inhibition of osteogenesis by down-regulating the expression of RUNX2 (72,73). Further, the expression of cartilage oligomeric matrix protein/angiopoietin1 (COMP/ANGPT1), which promotes osteogenic differentiation (74), was inhibited by space microgravity. In addition, space microgravity promoted the expression of mesenteric estrogen dependent adipogenesis, leucine rich repeat containing 8 VRAC subunit C, and Bardet-Biedl syndrome 4, genes that have been confirmed to promote adipogenic differentiation (75)(76)(77).…”

Identifying the Cellular Mechanisms Leading to Heterotopic Ossification

“…Recent evidence published by identified that Ang1/Tie2 signalling in MSC cultures led to a strongly osteochondrogenic phenotype, further identifying a link between endothelial cells and the pathological process of ectopic bone formation [85]. Furthermore, there is evidence to indicate that the expression of the endothelial Tie2 receptor is increased during osteogenesis and that treatment with angiopoietin 1 (Ang1), a growth factor involved in the production of stable vasculature, enhanced osteogenesis by potentiating the effects of BMP2 on MSCs [86].…”