Effects of Leptin, Platelet-Rich Plasma (PRP)---Calcium Phosphate Scaffold on Mscs and Osteoclast

Platelet-rich plasma (PRP) contains a number of these growth factors in its natural composition and has relevance in tissue engineering applications. However, the effects of PRP on mesenchymal stem cell (MSC) and osteoclast are still controversial. Wnt signaling could be used to stimulate bone healing and fracture repair. The canonical Wnt 3a/β-catenin pathway is also present in platelets which negatively regulate platelet function. However, the effects of PRP on Wnt/β-catenin pathway in MSCs are not clear. Leptin has a significant effect of promoting osteogenesis and inhibiting adipogenesis in MSCs. PRP improved proliferation but not osteogenic differentiation of MSCs which cultured on β-TCP scaffold. Our previous data showed that more expression of leptin receptor (Leptin-R) in β-TCP culture than in HA culture. Platelet pre-incubation with leptin led to a significant increase in platelet aggregation. However, the effects of leptin combined with PRP treatment on osteogenesis of MSCs are not clear. Exposure to HBO induces both platelet aggregation and protein release. Our previous study suggested that HBO up-regulates the expression of PDGF-β receptor in chondrocyte. HBO increased the osteogenic differentiation of MSCs by regulating Wnt3a/β-catenin signaling. However, the effects of HBO combined with PRP treatment on Wnt/β-catenin pathway in MSCs are not clear. MicroRNA emerged as an important regulator of developmental osteogenic signaling pathways, osteoblast growth and differentiation, osteoclast-mediated bone resorption activity and bone homeostasis in the adult skeleton. MicroRNA-29, 135, 138, and 335-5p reportedly regulate osteoblast differentiation. miR-21 and miR-155 have a positive effect by decreasing the levels of inhibitory genes, whereas miR-146a and miR-223 tend to impair osteoclast differentiation. Previous studies have determined a link between oxygen tension and regulation of microRNAs. The hypoxia up-regulated group includes miR-21 and 210 and down-regulated group includes miR-15b, 16, and 185. β-catenin has direct inhibitory effects on osteoclast precursors and NFATc1 plays a key role in RANKL-induced osteoclast activation. The effects of HBO or PRP treatment on microRNA profile expression in MSCs and osteoclast and NFATc1 expression in osteoclast are not clear. In the 1st year of this study, we will find the effects of PRP and leptin on MSCs via Wnt signaling regulation. In the 2nd year, we will find the potential effects of HBO and PRP on MicroRNA profiling in MSCs. In the 3rd year, we will find the effects of PRP and HBO on miRNA profile and NFATc1 expression in osteoclasts.

Project ID:PC10308-1426
External Project ID:MOST103-2314-B182A-111-MY3