Table 1. Key miRNA regulators of bone organogenesis and homeostasis.
| MiRNA biogenesis | Regulatory function | Activity | Strategy for reduced expression | Reference |
|---|---|---|---|---|
| Ago2 | Essential for development | Knockout inhibits osteoclast development | siRNA (in vitro) | 13 |
| DGCR8 | Essential for development | Knockout inhibits osteoclast development | CTSK-Cre, siRNA (in vitro) | 13,16 |
| Dicer | Essential for development | Knockout inhibits osteoblast, osteoclast, chondrocyte development | Col1a1-Cre, osteocalcin-Cre, CD11b-Cre, CTSK-Cre, Col2a1-Cre | 11,15 |
| Regulatory function | Activity | Targets | Reference | |
| Osteoclast | ||||
| MiR-21 | Activates | Promotes differentiation | PDCD4 | 14 |
| MiR-29b | Activates and/or inhibits | Activates and/or inhibits differentiation | Cdc42, Srgap2, Fos, Mmp2 | 26,27 |
| MiR-31 | Essential for development | Essential for differentiation | Rhoa | 28 |
| MiR-34a | Activates | Promotes differentiation | Tgif2 | 33 |
| MiR-125a | Inhibits | Inhibits differentiation | TRAF6 | 30 |
| MiR-146a | Inhibits | Inhibits differentiation, protects joint destruction during collagen-induced arthritis | 64 | |
| MiR-148a | Activates | Promotes differentiation | MAFB | 65 |
| MiR-155 | Inhibits | Inhibits differentiation | SCOS1, MITF | 31,32 |
| MiR-223 | Activates and/or inhibits | Positive and negative regulator of differentiation | 13,25 | |
| MiR-503 | Inhibits | Inhibits differentiation | RANK | 29 |
| Osteoblast | ||||
| MiR-15b | Activates | Promotes differentiation | Smurf1 | 66 |
| MiR-17∼92 | Activates | Promotes proliferation and differentiation | 67 | |
| MiR-17-5p, miR-106 | Inhibits | Inhibits differentiation | BMP2 | 68 |
| MiR-20a | Activates | Promotes differentiation | PPARγ, Bambi, Crim1 | 69 |
| MiR-23a/27a/24-2 | Inhibits | Inhibits apoptosis | FAK, Runx2, Satb2 | 21,22 |
| MiR-29a | Activates | Promotes differentiation | Osteonectin, Dkk1, Kremen2, sFRP2 | 70,71,72 |
| MiR-30c | Inhibits | Inhibits differentiation | Smad1, Runx2 | 21 |
| MiR-34c | Inhibits | Inhibits proliferation and differentiation | SATB2, Runx2, Notch pathway | 21,34,35 |
| MiR-93 | Inhibits | Inhibits mineralization | Sp7/Osx | 73 |
| MiR-100 | Inhibits | Inhibits differentiation | BMPR2 | 74 |
| MiR-125b | Inhibits | Inhibits differentiation | ErbB2, Sp7/Osx | 75,76 |
| MiR-133a | Inhibits | Inhibits differentiation | Runx2 | 21 |
| MiR-135a | Inhibits | Inhibits differentiation | Runx2 | 21 |
| MiR-137 | Inhibits | Inhibits differentiation | Runx2 | 21 |
| MiR-138 | Inhibits | Inhibits differentiation | FAK, indirectly Sp7/Osx | 24 |
| MiR-141, miR-200a | Inhibits | Inhibits differentiation | Dlx5 | 77 |
| MiR-143 | Inhibits | Inhibits differentiation | Sp7/Osx | 78 |
| MiR-155 | Inhibits | Regulates TNFα inhibition of osteoblast differentiation | SOCS1, MITF | 31 |
| MiR-181a | Activates | Promotes differentiation | Tgfbr1, Tgfbi | 79 |
| MiR-182 | Inhibits | Inhibits proliferation and differentiation | Foxo1 | 80 |
| MiR-204/211 | Inhibits | Inhibits differentiation | Runx2, Sost | 21 |
| MiR-205 | Inhibits | Inhibits differentiation | Runx2 | 21 |
| MiR-206 | Inhibits | Inhibits differentiation | Cx43 | 23 |
| MiR-208 | Inhibits | Inhibits differentiation | Ets1 | 81 |
| MiR-214 | Inhibits | Inhibits activity and bone formation | ATF4, Sp7/Osx | 82,83 |
| MiR-217 | Inhibits | Inhibits differentiation | Runx2 | 21 |
| MiR-218 | Inhibits | Inhibits differentiation | Runx2, Dkk2, Sfrp2 | 21 |
| MiR-322 | Activates | Promotes differentiation | Tob2, indirectly Sp7/Osx | 84 |
| MiR-335-5p | Activates | Promotes differentiation | DKK1 | 85 |
| MiR-338 | Inhibits | Inhibits differentiation | Runx2 | 21 |
| MiR-542-3p | Inhibits | Inhibits differentiation | BMP7 | 86 |
| MiR-637 | Inhibits | Inhibits differentiation | Sp7/Osx, Col4a1, Bmp2k | 87,88 |
| MiR-764-5p | Inhibits | Inhibits differentiation | CHIP/STUB1 | 89 |
| Regulatory function | Activity | Targets | Reference | |
| Chondrocytes | ||||
| Let-7 | Activates | Promotes proliferation | Cdc34, E2f5 | 90 |
| MiR-17–92 | Essential for development | Loss induces microcephaly and other skeletal defects in patients | 91 | |
| MiR-34a | Inhibits | Inhibits differentiation | Apoptosis | 92,93 |
| MiR-140 | Essential for activity | Essential for proper activity | Sp1, HDAC4, Pdgfra, Dnpep,Smad3, Rala | 17,18 |
| MiR-145 | Inhibits | Inhibits differentiation | Sox9 | 20 |
| MiR-199a* | Inhibits | Inhibits differentiation | Smad1 | 19 |
| MiR-221 | Inhibits | Inhibits proliferation | Mdm2 | 94 |
| MiR-335 | Activates | Promotes differentiation | Rock1, Daam1 | 95 |
| MiR-337 | Inhibits | Inhibits differentiation | Tgfbr2 | 96 |
| MiR-449 | Inhibits | Inhibits differentiation | Lef1 | 97 |
| MiR-1247 | Inhibits | Inhibits differentiation | Sox9 | 98 |
Abbreviations: Ago2, argonaute; DGCR8, double-stranded RNA-binding protein Pasha; miR, microRNA; siRNA, small interfering RNA; TNFα, tumor necrosis factor-α.