Review Article

Exosome-Derived Noncoding RNAs as a Promising Treatment of Bone Regeneration

Table 1

Reported roles of exosomal ncRNAs in osteogenesis.

Origin of exosomesExperimental objectiveContent analysisPotential targetsIn vitro effectIn vivo effect

MSCsTo identify the exosomal microRNA profiles in different osteogenic differentiation stages of MSCsmiR-31, miR-221, and miR-144 were decreased in exosomes from the late stage of osteogenic differentiation; miR-21 was upregulated.miR-31: Osterix (Osx) and special AT-rich sequence-binding protein 2 (Satb2); miR-221: Runx2; miR-144; Smad4; miR-21: pry1, Sox2, Smad7Exosomes derived from hMSCs induce osteogenic differentiation of hMSCs in a stage-dependent mannerā€”
MyoblastTo study the cross-talk between muscle and bonemiR-27a-3pApc, a negative regulator of b-catenin; Atf3Myoblast exosomes affect the osteogenic differentiation of preosteoblasts
PreosteoblastsTo elucidate the effect of exosomal miRNAs on preosteoblast differentiationLet-7 miRNAThe high-mobility group AT-hook 2 (Hmga2)Exosomes whose let-7 was inactivated efficiently lost their osteogenic differentiation capacity.
OsteoblastsTo study the effect of the exosomes derived from mineralizing osteoblasts on the osteogenic differentiation of MSCs.miR-667-3p, miR-6769b-5p, miR-7044-5p, miR-7668-3p, and miR-874-3pAxin1, an important negative regulator of Wnt signaling pathwayExosomes from MC3T3- E1 under 21 days of osteogenesis induction promote bone marrow stromal cell differentiation to osteoblasts
BMSCsTo identify the miRNA profile in exosomes derived from aged micemiR-183 cluster (miR-96/-182/-183)Heme oxygenase-1 (Hmox1)Aged exosomes inhibit the osteogenic differentiation of BMSCs
BMSCTo study the underlying mechanism of MSCT ameliorating osteopenia in Fas-deficient-MRL/lpr micemiR-29bDnmt1Improved osteogenic differentiation of MSCs from systemic lupus erythematosus (SLE) modelInfusing exosomes rescues osteoporotic phenotype
Adipose mesenchymal stem cells (ASCs)To investigate whether exosomes derived from miR-375-overexpressing hASCs could enhance bone regenerationmiR-375Insulin-like growth factor-binding protein 3 (lgfbp3)Improved the osteogenic differentiation of hBMSCsEnhanced the bone regeneration in calvarial defect
Multiple myeloma (MM)--MSCsTo understand the myeloma-stroma interactionsRUNX-AS1Runx2Exosomes from MM-MSCs impaired the osteogenic differentiation of MSCsInhibitor of exosome secretion, prevented bone loss in MM
BMSCTo characterize the full small RNAome of MSC-produced exosomes5 halves of tRNARunx2, Sox11, Smad3