Table 4.
ncRNAs in MSC aging and related diseases.
| Regulatory factors | Mechanism | In vivo or in vitro | Consequence | Material | Ref. |
|---|---|---|---|---|---|
| Senescence and aging | |||||
| miR-10a↓ | Insufficient to target Klf4 and repress its function | Both | Senescence, decreased differentiation | hBMSCs | [74, 75] |
| miR-20b-5p and miR-106a-5p↓ | Insufficient to inhibit Smads/p21/CDK/E2F pathway, which alleviates suspension of DNA synthesis during oxidative stress-induced premature senescence | In vitro | Premature senescence | hBMSCs | [77] |
| miR-22 and miR-485-5p↑ | Targets CKS1 to downregulate CDK1 and cyclin B | In vitro | Senescence | SHED | [69] |
| miR-31a-5p↑ | Targets E2F2 and promotes SAHF formation | Both | Senescence | Rat BMSCs | [71] |
| miR-27b↑ | Upregulates p16 expression and MAPK pathway activation | In vitro | Senescence | Pig ADSCs | [98] |
| miR-29c-3p↑ | Targets CNOT6 thus inducing senescence via p53/p21 and p16/pRB pathways | In vitro | Senescence | hBMSCs | [72, 73] |
| miR-34a↑ | Reduces CDK2, CDK4, CDK6, and cyclin D and E expression to hinder the SOX2-related self-renewal ability | In vitro | Senescence | hADSCs | [70] |
| miR-34a↑ | Targets Sirt1 to induce senescence via Sirt1/FoxO3a pathway, induces mitochondrial dysfunction | In vitro | Senescence and intrinsic apoptosis | Mouse BMSCs, rat BMSCs | [89, 90] |
| miR-141-3p↑ | Targets Zmpste24 transcripts, causing prelamin A accumulation in nuclear envelope and intracellular DNA damage | In vitro | Senescence | hUCSCs | [92] |
| miR-141-3p↑ | Targets YAP to inhibit proliferation and accelerate senescence | In vitro | Senescence | Human papilla apical stem cells | [93] |
| miR-142↑ | Targets Epas1 to downregulate pexophagic activity and induce ROS accumulation | In vitro | Aging | Mouse BMSCs | [81] |
| miR-155-5p↑ | Targets Cab39 and then reduces mitochondrial fission and increases mitochondrial fusion via the Cab39/AMPK signaling pathway | Both | Aging | Mouse model, hBMSCs | [86] |
| miR-155-5p↑ | Targets Bag5 that encodes partner protein of PINK1, to inhibit mitophagy and dysfunctional mitochondria elimination | In vitro | Aging | hBMSCs | [87] |
| miR-155-5p↑ | Targets the common transcription factor C/EBP-β thus repressing antioxidant genes and inducing ROS production | Both | Aging | hBMSCs/mouse BMSCs | [82] |
| miR-182↑ | Targets FoxO1, which is critical to protecting cells from ROS | In vitro | Aging, decreased proliferation, and osteogenesis | hBMSCs | [83] |
| miR-183-5p↑ | Targets Hmox-1 to impair response to oxidative stress | In vitro | Senescence | Mouse BMSCs | [84] |
| miR-188↑ | Targets HDAC9 and RICTOR | Both | Aging, decreased proliferation | Mouse BMSCs, mouse model | [94, 95] |
| miR-195↑ | Targets Tert and prevents TERT to repair the shortened telomeres with replication | In vitro | Aging | Mouse BMSCs | [91] |
| miR-199b-5p↓ | Insufficient to repress LAMC1 | In vitro | Senescence | hBMSCs | [80] |
| miR-206↑ | Targets Alpl, which is essential for the intracellular ATP level and AMPK pathway | Both | Premature senescence | Rat BMSCs, rat model | [96] |
| miR-363-3p↑ | Targets TRAF3, which inhibits adipogenic differentiation and senescence | In vitro | Senescence, upregulated adipogenesis | Rat BMSCs | [99] |
| miR-486-5p↑ | Targets Sirt1 | In vitro | Senescence | hADSCs | [85] |
| miR-543 and miR-590-3p↓ | Insufficient to target AIMP3/p18 to inhibit expression, inducing an increase in CDK inhibitors p16INK4A and p21CIP1/WAF1 | In vitro | Senescence | hUCSCs | [78] |
| miR-1292↑ | Targets Wnt receptor FZD4, thus hindering the Wnt/β-catenin/TCF/LEF1 pathway | In vitro | Senescence, downregulated osteogenesis | hADSCs | [100] |
| lncRNA-Bmncr↓ | Insufficient to serve as a scaffold to facilitate the interaction of ABL and transcriptional coactivator with TAZ, hindering the assembly of the TAZ and RUNX2/PPARγ transcriptional complex | Both | Aging, transition from osteogenesis to adipogenesis | hBMSCs, mouse BMSCs | [103] |
| lncRNA-HOTAIR↑ | Modulates senescence-associated changes in gene expression and DNA methylation via triple helix DNA-DNA-RNA formation | In vitro | Senescence | hBMSCs | [102] |
| Skeletal diseases | |||||
| miR-21↓ | Insufficient to target Spry1, which negatively regulates osteogenesis via FGF and MAPK | Both | Osteoporosis | hBMSCs, mouse model | [112] |
| miR-21a↓ | Insufficient to target Pten and PTEN downregulates AKT pathway to induce osteocyte apoptosis | Both | Glucocorticoid-induced osteonecrosis | hUCSCs, mouse model | [116] |
| miR-23b↑ | Targets Runx2 | Both | Osteoporosis | hBMSCs, mouse model | [106] |
| miR-27↓ | Insufficient to target Mef2c, which facilitates the adipogenic differentiation | Both | Osteoporosis | hBMSCs, mouse model | [113] |
| miR-181a↓ | Leads to the accumulation of FasL from BMSCs, followed by CD4+ T cell apoptosis | Both | Osteoporosis | Mouse BMSCs, mouse model | [115] |
| miR-212 and miR-384↑ | Targets Runx2 | Both | Osteoporosis | Mouse BMSCs, mouse model | [108] |
| miR-542-3p↓ | Insufficient to inhibit sFRP1 expression, which is a negative regulator of Wnt pathway | Both | Osteoporosis | HEK293T cells, rat BMSCs, rat model | [111] |
| miR-596↑ | Targets Smad3 to inhibit Runx2 expression and osteogenesis | In vitro | ONFH | hBMSCs | [109] |
| miR-705 and miR-3077-5p↑ | Respectively, targets HOXA10 and Runx2 mRNA, leading to MSC lineage commitment transition to adipocytes | In vitro | Osteoporosis | hBMSCs | [107] |
| miR-708↑ | Targets Smad3 to inhibit Runx2 expression | In vitro | ONFH | hBMSCs | [110] |
| miR-1263↓ | Insufficient to suppress Mob-1/YAP/Hippo signaling pathway-induced apoptosis | Both | Disused osteoporosis | hUCSCs, rat model | [114] |
| lncRNA-MALAT1↓ | Insufficient to inhibit miR-143, whose target is Osx | In vitro | Osteoporosis | hBMSCs | [117] |
| lncRNA-ORLNC1↑ | Endogenously competes with miR-296 and eliminates miR-296's suppression of Pten, which is a negative regulator of osteogenesis | Both | Osteoporosis | hBMSCs, mouse model | [119] |
| lncRNA-DEPTOR↑ | Binds to ncRNA-MEG3's promoter and reduces its function to activate BMP4 pathway | Both | Osteoporosis | Mouse BMSCs, mouse model | [120] |
| lncRNA-H19↓ | Insufficient to inhibit MSC proliferation and osteogenic differentiation via suppressing miR-19b-3p | In vitro | Inhibits osteoporosis | hBMSCs | [121] |
| lncRNA-HOTAIR↑ | Suppresses miR-17-5p to elevate Smad7 pathway | In vitro | Inhibits ONFH | hBMSCs | [122] |
ABL1: oncogene homolog 1; AIMP3: aminoacyl-tRNA synthetase-interacting multifunctional protein-3; CKS1: cyclin-dependent kinase regulatory subunit 1; Mef2c: myocyte enhancer factor 2c; LAMC1: laminin gamma 1; PRC2: polycomb repressive complex 2; SAHF: senescence-associated heterochromatin foci; sFRP1: secreted Frizzled-related protein-1; Spry1: sprouty homolog 1.