Application of exosome-derived noncoding RNAs in bone regeneration:Opportunities and challenges

With advances in the fields of regenerative medicine,cell-free therapy has received increased attention.Exosomes have a variety of endogenous properties that provide stability for molecular transport across biological barriers to cells,as a form of cell-to-cell communication that regulates function and phenotype.In addition,exosomes are an important component of paracrine signaling in stemcell-based therapy and can be used as a stand-alone therapy or as a drug delivery system.The remarkable potential of exosomes has paved the pathway for cell-free treatment in bone regeneration.Exosomes are enriched in distinct noncoding RNAs(ncRNAs),including microRNAs,long ncRNAs and circular RNAs.Different ncRNAs have multiple functions.Altered expression of ncRNA in exosomes is associated with the regenerative potential and development of various diseases,such as femoral head osteonecrosis,myocardial infarction,and cancer.Although there is increasing evidence that exosome-derived ncRNAs(exoncRNAs)have the potential for bone regeneration,the detailed mechanisms are not fully understood.Here,we review the biogenesis of exo-ncRNA and the effects of ncRNAs on angiogenesis and osteoblast-and osteoclast-related pathways in different diseases.However,there are still many unsolved problems and challenges in the clinical application of ncRNA;for instance,production,storage,targeted delivery and therapeutic potency assessment.Advancements in exo-ncRNA methods and design will promote the development of therapeutics,revolutionizing the present landscape.