Proteins extracted from placenta regulate osteogenic differentiation of human mesenchymal stem cells

Placenta is a medical waste, but the human placenta-derived proteins (hPDPs) have highly significant application value. The precise mechanism of injectable hPDPs gel on bone regeneration has been scarcely studied. In this study, a succinct methodology was employed to extract all proteins in the placenta. Proteomic analysis revealed that key gene ontology (GO) terms, signaling pathways, and osteogenic stimulators in PDPs, such as THY1, GDF15, SPARC, GPNMB, PARK7, EFEMP1, and LRP. In order to provide evidence supporting the ability of injectable hPDPs to promote osteogenesis and osteogenic differentiation (OD), the in vitro experiments utilizing human mesenchymal stem cells (hMSCs) and in vivo heterotopic osteogenesis animal models were conducted to assess the bone-forming ability of hPDPs. Results demonstrated that hPDPs accelerated OD of hMSCs and enhanced osteogenesis. Proteomic data, qPCR, immunofluorescence (IF) staining, RNA-sequencing data, KEGG, and GO enrichment analysis were utilized to elucidate the mechanisms underlying hPDP-induced OD. The findings indicated that the PDPs could promote OD through the activation of osteogenic stimulators and multiple signaling pathways, especially the BMP2/TGF-β signaling pathway and the iron metabolism pathway. This research elucidated the function and mechanism of PDPs in OD, providing valuable insights into their potential clinical applications. The findings suggest a novel strategy for utilizing medical waste or their stimulators as biocompatible materials for bone tissue engineering applications.