MicroRNA biogenesis and regulation of bone remodeling

Kapinas, Kristina; Delany, Anne M

doi:10.1186/ar3325

Arthritis Research & Therapy

Table 1 Summary of microRNAs, their targets, expression, and effects on osteoblast differentiation

From: MicroRNA biogenesis and regulation of bone remodeling

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.

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