Exosomes derived from human platelet-rich plasma prevent apoptosis induced by glucocorticoid-associated endoplasmic reticulum stress in rat osteonecrosis of the femoral head via the Akt/Bad/Bcl-2 signal pathway

Abstract

An excess of glucocorticoids (GCs) is reported to be one of the most common causes of osteonecrosis of the femoral head (ONFH). In addition, GCs can induce bone cell apoptosis through modulating endoplasmic reticulum (ER) stress. Among the three main signal pathways in ER stress, the PERK (protein kinase RNA-like ER kinase)/CHOP (CCAAT-enhancer-binding protein homologous protein) pathway has been considered to be closely associated with apoptosis. Platelet-rich plasma (PRP) has been referred to as a concentration of growth factors and the exosomes derived from PRP (PRP-Exos) have a similar effect to their parent material. The enriched growth factors can be encapsulated into PRP-Exos and activate Akt and Erk pathways to promote angiogenesis. Activation of the Akt pathway may promote the expression of anti-apoptotic proteins like Bcl-2, while CHOP can inhibit B-cell lymphoma 2 (Bcl-2) expression to increase the level of cleaved caspase-3 and lead to cell death. Consequently, we hypothesized that PRP-Exos prevent apoptosis induced by glucocorticoid-associated ER stress in rat ONFH via the Akt/Bad/Bcl-2 signal pathway. To verify this hypothesis, a dexamethasone (DEX)-treated in vitro cell model and methylprednisolone (MPS)-treated in vivo rat model were adopted. Characterization of PRP-Exos, and effects of PRP-Exos on proliferation, apoptosis, angiogenesis, and osteogenesis of cells treated with GCs in vitro and in vivo were examined. Furthermore, the mechanism by which PRP-Exos rescue the GC-induced apoptosis through the Akt/Bad/Bcl-2 pathway was also investigated. The results indicate that PRP-Exos have the capability to prevent GC-induced apoptosis in a rat model of ONFH by promoting Bcl-2 expression via the Akt/Bad/Bcl-2 signal pathway under ER stress.

Icariin promotes angiogenesis in glucocorticoid‐induced osteonecrosis of femoral heads: In vitro and in vivo studies

“…Apoptosis is a normal physiological process that plays an essential role in the progression of ONFH . The endothelium is a crucial site where the control of apoptosis during angiogenesis occurs .…”

Effect of platelet‐rich plasma on proliferation and migration in human dermal fibroblasts

“…Moreover, a recent study showed that PRP promotes the proliferation of HDFs through the activation of ERK1/2 signaling; this was shown by the fact that PRP promotes ERK1/2 phosphorylation, whereas ERK1/2 inhibition eliminates the increase in proliferation triggered by PRP . It has been reported that PRP‐derived exosomes promote cell proliferation by regulating apoptosis through Akt signaling …”

Microfluidics‐based on‐a‐chip systems for isolating and analysing extracellular vesicles

“…Moreover, MSC-derived EVs may induce angiogenesis in ischaemia-related disease [44]. The potential of human platelet-derived EVs in tissue regeneration is also emerging [18,45,46]. …”