Exosome: A Novel Nanocarrier Delivering Noncoding RNA for Bone Tissue Engineering

Table 1

List of miRNA deliveries by exosome in both basic and clinical research of bone formation.

miRNA	Target gene	Resource	Recipient cells	Mechanism and result	Ref.
miR-128-3P	Smad5	MSCs	MSCs	miR-128-3p was highly expressed in aged exosome, inhibiting fracture healing by targeting Smad5.	[48]
miR-221-3p		CPCs	Murine chondrocytes	In vivo experiments confirmed that miR-221-3p was highly enriched in CPCs-Exos, which can stimulate chondrocyte proliferation and migration.	[49]
miR-140		Freeze and thaw method	BMSCs	miR-140 was fused into exosomes by freezing and thawing, promoting the differentiation of BMSCs into chondrocytes.[	[50]
miR-1263	Mob1	HUC-MSCs	BMSCs	Exosomes inhibit BMSC apoptosis through miR-1263/Mob1/Hippo signaling pathway.	[51]
miR-8485	DACT1, GSK3B	Chondrocytes	BMSCs	Exosomal miR-8485 regulated the Wnt/β-catenin pathways to promote chondrogenic differentiation of BMSCs.	[52]
miR-192-5p	RAC2	BMSCs		The exosomal miR-192-5p of BMSCs can delay the inflammatory response of rheumatoid arthritis by regulating the expression of proinflammatory factors.	[53]
miR-375	IGFBP3	hASCs	BMSCs	Exosomes derived from hASCs overexpressing miR-375 promoted bone regeneration by binding to IGFBP3.	[84]
miR-26a-5p	PTGS2	BMSC	Synovial fibroblasts	The hBMSC-derived exosome- miR-26a-5p inhibited the damage of synovial fibroblasts by targeting PTGS2.	[85]
miR-155		VECs	Macrophages	VEC-Exos was rich in miR-155, which indirectly inhibited osteoclast activity by interacting with macrophages to improve the symptoms of osteoporosis.	[86]
miR-129-5p	Sp1	MMs	hMSCs	Multiple myeloma (MM) exosome miR-129-5p reduced alkaline phosphatase (ALPL) activity by inhibiting the expression of transcription factor Sp1 in hMSCs.	[87]
miR-17	RANKL	Keratinocytes	Osteoclasts	The exosomal miR-17 secreted by keratinocytes with middle ear cholesteatoma can upregulate RANKL in fibroblasts and induce osteoclast differentiation.	[30]

MSCs: mesenchymal stem cells; BMSCs: bone marrow mesenchymal stem cells; HUC-MSCs: human umbilical cord mesenchymal stem cells; hASCs: human adipose mesenchymal stem cells; VECs: vascular endothelial cells; CPCs: chondrogenic progenitor cells; MMs: multiple myelomas.