Table 5.
The roles of mechanosensitive miRNAs in bone formation.
| miRNAs | Mechanical Methods | Source | Supporting Observations | Reference |
|---|---|---|---|---|
| miR17-92 cluster | four-point bending device at 2 Hz for 36 cycles for 2 weeks | Osteoblast cKO mice | Block tibia periosteal bone formation response to mechanical exercise loading in the cKO mice; alveolar bone size and incisor tooth mechanical properties decreased in the cKO mice. | [72,73,75] |
| miR-222 | anterior weight-bearing and posterior non–weight-bearing regions | bovine articular cartilage | A potential regulator of an articular cartilage mechanotransduction pathway. | [74] |
| miR-21 | orthodontic force in periodontal tissue at 30 g of force for 7 d | miR-21−/− mice | miR-21 deficiency prevented force-induced alveolar bone formation just in the tensile side, while blocking bone resorption in both the compressive and tensile sides. | [76] |
| miR-503-5p | the left maxillary first molars were mesially stretched at 50 g of force for 1, 3, 7, 14 d respectively | alveolar bones | Agomir-503-5p decreased Runx2, Alp mRNA and protein expression, decreased osteoblast numbers and osteoblastic bone formation in the orthodontic tooth movement (OTM) tension sides. | [22] |
| miR-188 | 3, 6, 12, 18-month mice 85 human females and 85 males at different ages |
BMSCs | miR-188 level increased with age. Further, miR-188 deficiency revealed substantially reduced decrease of age-associated rates of bone formation and tibia maximum mechanical load; miR-188 transgenic mice determined opposite results; miR-188 inhibitor via a BMSC-specific aptamer relieved age-induced osteoporosis and reduction of femur maximum mechanical load. | [84] |
| miR-214 | 20 human females and 20 males at different ages | Bone specimens | Expression of miR-214 increased with age and was negatively correlated with the expressions of bone formation marker genes. | [85] |
| miR-142-5p | Mice at 10 weeks and 18 months of age | Bone callus | miR-142-5p level was lower in the callus of aged mice than the young group, and Agomir-142-5p repaired the aged bone fractures. | [86] |
| miR-31 | Mice at 2, 8, 25 months of age | MSCs and bone tissue | miR-31 level showed a consistent decreased trend with age increasing in MSCs and bone. | [83] |
| miRNAs | Mechanical Methods | Source | Functions | Reference |
| miR17-92 cluster | Mice at 4 and16 months of age | BMSCs and bone tissue | miR-17 mimics could partially rescue the osteogenesis of old MSCs both in vitro an in vivo | [82] |
| miR-let-7f, -199-3p, -125b, -222 | 22 healthy rhesus macaques young (<5 years), middle (8–10 years), old (>12 years, n = 9) |
BMSCs | Analysis of miRNA expression profiles and qPCR results revealed a down-regulation of miR-let-7f, miR-125b, miR-222 and miR-199-3p in old rBMSCs. | [87] |
| miR-103-3p, -30b-5p, -142-3p | 10-degree head-down tilt position for 42-day long-duration bedrest | serum of rhesus monkeys | Expressions of the three miRNAs declined in the serum of rhesus monkeys after bedrest and positively correlated with BMD. | [90] |
| miR-103, -130a, -1234, -1290, -151-5p, -151-3p, -199a-3p, -20a, -148a, -363, -451a | 16 male volunteers after 45 days of −6° head-down tilt bedrest | plasma of individuals | These miRNAs were dramatically decreased after 45 days of bedrest, while the expressions of these miRNAs were recovered after 10 days of recovery, except miR-148a, 199a-3p and 151-3p. Additionally, several miRNAs especially miR-1234 was identified in positive correlation with bone formation parameters. | [91] |
| miR-214 | Hind-limb unloading for 28 days | Alp+ cells and bone tissue | miR-214 level was up-regulated after 28-day hind-limb unloading, and Antagomir-214 counteracts unloading induced bone loss. | [85] |
| miR-103a | Hind-limb unloading for 28 days | bone tissue | Antagomir-103a partly resumed unloading-caused bone loss. | [23] |
| miR-139-3p, -339-3p, -132-3p, -487b, -2985, -34b | Hind-limb unloading for 21 days | bone tissue | the expression levels of miR-139-3p, -339-3p and -132-3p were up-regulated, and the expression levels of miR-487b, -2985 and -34b were down-regulated in rat bone after three weeks tail suspension. | [60] |
Alp: alkaline phosphatase; Alp+: Alp positive; BMD: bone mineral density; BMSCs: bone marrow mesenchymal stem cells; cKO: conditional knockout; d: days; miR: microRNA; MSCs: mesenchymal stem cells; OTM: Orthodontic tooth movement; Runx2: Runt related transcription factor 2.