Periostin: A Downstream Mediator of EphB4‐Induced Osteogenic Differentiation of Human Bone Marrow‐Derived Mesenchymal Stem Cells

Abstract

Erythropoietin-producing hepatocyte B4 (EphB4) has been reported to be a key molecular switch in the regulation of bone homeostasis, but the underlying mechanism remains poorly understood. In this study, we investigated the role of EphB4 in regulating the expression of periostin (POSTN) within bone marrow-derived mesenchymal stem cells (MSCs) and assessed its effect and molecular mechanism of osteogenic induction in vitro. Treatment with ephrinB2-FC significantly increased the expression of POSTN in MSCs, and the inhibition of EphB4 could abrogate this effect. In addition, osteogenic markers were upregulated especially in MSCs overexpressing EphB4. To elucidate the underlying mechanism of cross talk between EphB4 and the Wnt pathway, we detected the change in protein expression of phosphorylated-glycogen synthase kinase 3β-serine 9 (p-GSK-3β-Ser9) and β-catenin, as well as the osteogenic markers Runx2 and COL1. The results showed that GSK-3β activation and osteogenic marker expression levels were downregulated by ephrinB2-FC treatment, but these effects were inhibited by blocking integrin αvβ3 in MSCs. Our findings demonstrate that EphB4 can promote osteogenic differentiation of MSCs via upregulation of POSTN expression. It not only helps to reveal the interaction mechanism between EphB4 and Wnt pathway but also brings a better understanding of EphB4/ephrinB2 signaling in bone homeostasis.

Periostin Upregulates Wnt/β-Catenin Signaling to Promote the Osteogenesis of CTLA4-Modified Human Bone Marrow-Mesenchymal Stem Cells

“…In bone tissue, POSTN is preferentially expressed by periosteal osteoblasts in response to mechanical stimulation or parathyroid hormone (PTH), bone morphogenetic protein (BMP)-2, and transforming growth factor (TGF)-β, and it can regulate the osteogenic differentiation of osteoblasts to enhance bone formation 28 . Our pervious study also confirmed that the activation of erythropoietin-producing hepatocyte receptors (Eph) B4 up-regulates POSTN expression in MSCs and plays a crucial role in regulating bone homeostasis through an unknown mechanism 29 . A recent study reported that POSTN interacts with the Wnt/β-catenin signaling pathway indirectly by inhibiting sclerostin expression in bone 30 .…”

The Impact of Anti-Epileptic Drugs on Growth and Bone Metabolism

“…The levels of total calcium, phosphorus, magnesium, and parathyroid hormone (PTH) were unaffected by BZDs [24,35] although some other results are controversial [45,46,47]. Interestingly, a report showed that midazolam could exert negative effects on cell viability and osteogenic differentiation of cultured human bone marrow stem cells, suggesting a detrimental effect of the use of midazolam on bone formation and growth [48] (Table 1). …”

Into the eyes of bone marrow-derived mesenchymal stem cells therapy for myocardial infarction and other diseases

“…Nowadays, selecting the appropriate factor based on different reactivity of BM-MSCs to growth factors, to stimulate the proliferation, obtaining a higher proportion the mesenchymal stem cells has been regarded as a more accurate isolation method. Meanwhile, the new method of using 3 microns diameter plastic petri dish to screen BMMSCs, whose homogeneity are greater than 98%, with capacity of proliferation, self-renewal and have the potential to differentiate into bone, fat, cartilage tissue differentiation nature (6,(16)(17)(18)(19)(20). Overall, currently methods are various among laboratories in the world and further standardization of the BM-MSCs' separation process is still needed indepth study according to their biological characteristics and mechanisms.…”