Table 1

Summary of microRNAs, their targets, expression, and effects on osteoblast differentiation

miRNA

Target gene(s)

Endogenous miRNA expression

miRNA over-expression

miRNA inhibition

Reference


125b

NR

Decreased in BMP4-induced osteoblastic differentiation of ST2 cells

Inhibits ALP activity

Increases ALP activity

[58]

133

Runx2

Decreased in BMP2-induced osteoblast differentiation of C2C12 cells

Decreases ALP and osteocalcin mRNA

NR

[49]

135

Smad5

141, 200a

Dlx5

Repressed by BMP in MC3T3-E1 cells

Inhibits ALP activity

Increases ALP activity

[54]

199a, 346

LIF

Increased during osteoblast differentiation of hMSCs

NR

NR

[46]

204

Runx2

Increased in C3H10T1/2 cells and hMSCs during adipogenesis

Enhances adipogenesis (increases oil red O staining, and AP2, adipsin, and PPARγ mRNA); inhibits osteoblastogenesis (decreases ALP activity, and ALP, osteopontin, and osteocalcin mRNA)

Enhances osteoblastogenesis (increases ALP activity, and ALP, osteopontin, and osteocalcin mRNA); inhibits adipogenesis (decreases oil red O staining, and AP2, adipsin, and PPARγ mRNA)

[61]

206

Connexin 43

Decreased in BMP2-induced osteoblastic differentiation of C2C12 cells; deceased during osteoblastic differentiation of primary mouse osteoblasts

Causes osteopenia in vivo; decreases osteocalcin and Runx2 mRNA, and ALP activity; increases myogenic markers (MyoD, Myf5)

Increases ALP activity

[52]

208

Ets1

Repressed by BMP treatment in MC3T3-E1 cells

Decreases ALP activity, Alizarin red staining, and osteopontin protein

No effect

[56]

210

AcvR1b

Increased in BMP4-induced osteoblastic differentiation of ST2 cells

Increases ALP, osteocalcin, and osterix mRNA, and ALP activity

Decreases osteocalcin mRNA

[59]

23a/27a/24-2

Runx2, SATB2

Increased during osteoblastic differentiation of rat primary osteoblasts

Decreases ALP activity and mRNA, vonKossa staining, Runx2, osterix, and osteocalcin mRNA

NR

[62]

26a

SMAD1

Increased during terminal osteoblastic differentiation in hADSCs

NR

Increases ALP, osteopontin, and osteocalcin mRNA

[63]

27

APC

Increased during osteoblastic differentiation of hFOB 1.19 cells

Increases ALP and osteocalcin mRNA; augments Wnt signaling

Decreases ALP and osteocalcin mRNA

[73]

2861

HDAC5

Increased in BMP2-induced osteoblastic differentiation of ST2 cells; enriched in human bone

Augments BMP-induced increase in osteocalcin mRNA

Decreases bone volume and BFR in vivo; patients homozygous for miR-2861 mutation have very low bone mass

[74]

29a, 29c

COL1A1, COL3A1, Osteonectin/SPARC, Kremen2, Dkk1, Sfrp2

Increased during osteoblastic differentiation in MC3T3-E1 cells, primary osteoblasts (human and mouse), and hFOB1.19 cells

Increases osteocalcin mRNA; potentiates Wnt signaling

Inhibits ALP and osteocalcin mRNA, and ALP activity; blunts Wnt signaling

[60,68,72]

29b

COL1A1, HDAC4, DUSP2, TGFβ3, AcvR2a, CTNNBIP1

Increased during osteoblastic differentiation in MC3T3-E1 cells

Increases ALP mRNA and ALP activity

NR

[70]

3960

Hoxa2

Increased in response to BMP-2 in mouse primary osteoblasts

Increases ALP, osteocalcin, and Runx2 mRNA

Decreases ALP, osteocalcin, and Runx2 mRNA

[76]


ALP, alkaline phosphatase; BFR, bone formation rate; BMP, bone morphogenetic protein; hADSC, human adipocyte derived stem cell; hMSC, human mesenchymal stem cell; miRNA, microRNA; NR, not reported; PPAR, peroxisome proliferator-activated receptor.

Kapinas and Delany Arthritis Research & Therapy 2011 13:220   doi:10.1186/ar3325