Table 1. Potential activity of candidate microRNAs in bone-related disease and aortic calcification.
MiRs | Target gene* (nucleotide site in 3’UTR) |
Regulatory function | In vitro and animal study | Clinical relevance | Ref |
---|---|---|---|---|---|
miR-26a-5p | -CTGF (38–44 ; 7 merA1) -BMP/SMAD1 (46–53 ; 8mer) (103–109 ; 7merA1) |
↓ in vascular diseases angiogenesis, myocardial infarct size and improve heart function ↓ osteoclastic differentiation |
↓ in rat cardiac hypertrophy ↓ vascular smooth muscle cell calcification ↓ calcification related-genes (BMP2, SMAD1,2, ALP) |
↓ in aortic valve calcification and stenosis | [33–37] |
miR-34a-5p | -PPP1R10 (822–828 ; 7–8 mer) -TGIF2 (90–97 ; 8 mer) -JAG1 (1302–1308 ; 7–8 mer) |
↑Age-induced cardiac cell death ↓Osteoclastogenesis ↓osteoblast differentiation |
↑ cardiac dysfunction after myocardial infarction ↓ bone resorption, bone mass ↓ in vivo bone formation of human stromal stem cells. |
Antagomir therapeutic improves aging cardiac dysfunctions and stimulates osteoblast differentiation Attenuates osteoporosis ↓ Therapeutic strategy for enhancing bone formation |
[38–41] |
miR-223 | -SCARB1 (575–582 ; 8 mer) -FCGR1A (141–147 ; 7–8 mer) -NFIA (811–818 ; 8 mer) |
↓ HDL-cholesterol uptake, biosynthesis, cholesterol efflux ↓proliferation and ↑ apoptosis in vascular wall ↑ Inorganic Phosphate-induced- osteoclastogenesis and osteoclast differentiation |
↑HDL-cholesterol, hepatic and total plasma cholesterol in KD mice ↑ in serum and atherosclerotic vascular walls ↓atherosclerotic lesions in mice ↓levels in serum, blood cells of chimeric-KD-mice Modulate the balance osteoblast-like/ osteoclast-like |
Biomarker for altered cholesterol homeostasis ↑levels in serum from Kawasaki disease ↓ in serum from patients with chronic kidney disease Treatment to reverse vascular calcification without altering bone structure in CKD-MBD Provide new therapeutic target for atherogenesis |
[42–47] |
*: The target genes are indicated with the nucleotide position of the seed region in the 3’-UTR (according to Target Scan). ↑ ↓ are for up- and -down regulation respectively.