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.

Hip survival rate in the patients with avascular necrosis of femoral head after transtrochanteric rotational osteotomy: a systematic review and meta-analysis

Background:The clinical outcome of transtrochanteric rotational osteotomy(TRO)for osteonecrosis of the femoral head(ONFH)remains controversial,and the promising clinical results of several Japanese studies could not be reproduced in American and European studies.Trying to solve controversies on TRO for ONFH rising from apparently conflicting studies,a meta-analysis was conducted to assess the 5-and 10-year hip survival rates(with conversion to artificial joint replacement and radiographic failure as endpoints)after TRO.Methods:All eligible studies were searched in seven comprehensive databases including PubMed,Web of Science,Embase,Cochrane Library,VIP Database,China Knowledge Resource Integrated Database,and Wan Fang Database prior to June 2019.The outcomes evaluated were 5-and 10-year hip survival rates after TRO.The odds ratio and risk difference for the noncomparative binary data with the 95%confidence intervals(CIs)were calculated for each outcome.The included studies were assessed for methodologic bias and potential reasons for heterogeneity were explored.Results:Nineteen studies of TRO for ONFH were eligible for this meta-analysis according to inclusion criteria.Based on the previous report,two calculation methods(Methods 1 and 2)were adopted in this meta-analysis.Furthermore,we performed a subgroup analysis of the 5-and 10-year hip survival rates(Method 1)after TRO for ONFH:Asian sub-population and non-Asian subpopulation.Taking conversion to artificial joint replacement as the endpoint,5-and 10-year hip survival rates(Method 1)after TRO for ONFH in the Asian population were 0.86(95%CI=0.82–0.89)and 0.72(95%CI=0.65–0.78),respectively,and 5-and 10-year hip survival rates after TRO for ONFH in the non-Asian population were 0.55(95%CI=0.43–0.67)and 0.42(95%CI=0.28–0.55),respectively.The 5-and 10-year hip survival rates(Method 2)after TRO for ONFH were 0.90(95%CI=0.79–0.95)and 0.89(95%CI=0.81–0.94),respectively.Taking radiographic failure as the endpoint,5-and 10-year hip survival rates after TRO for ONFH were 0.70(95%CI=0.64–0.76)and 0.53(95%CI=0.46–0.61),respectively.Conclusions:The 5-and 10-year hip survival rates after TRO for ONFH were satisfactory in the Asian population,and were acceptable in the non-Asian population despite high early failure rates.