Noncoding RNAs in Steroid-Induced Osteonecrosis of the Femoral Head

Table 2

Functions of the miRNAs in steroid-induced ONFH.

Evaluated miRNA(s)	Study type	Involved cells/in vivo model/clinical samples	Target(s)	Pathway	Functions	Dysregulation (up/down)	Species	References
miR-20b	In vivo	Osteocytes and rat	BMP	BMP	Block the angiogenesis in bone tissues, promoting osteocyte apoptosis	Up	Rat	[26]
miR-7	In vitro	Osteoblasts	EGFR	EGFR/Akt	Promote osteoblast death	Up	Human	[56]
miR-217	In vitro	BMSCs	DKK1	—	Promote cell proliferation and osteogenic differentiation	Down	Human	[27]
miR-27a	In vivo and vitro	Preosteoblasts and rat	TGF-β and Smad7	TGF-β/Smad7	Promote osteogenic differentiation and increase proliferation	Down	Human and rat	[28]
	In vivo and vitro	mBMSCs and rat	PPARγ and GREM1	PPARγ	Suppress adipogenesis and enhance osteogenesis	Down	Rat	[21]
miR-320	In vivo and in vitro	Human ONFH tissue and rat	CYP1A2	—	Inhibit the occurrence and development of ONFH	Down	Human and rat	[29]
miR-206	In vitro	Osteoblasts	PDCD4	—	Decrease cell viability and proliferation, while apoptosis was induced	Up	Human	[30]
	In vivo and in vitro	Osteoblasts and rabbit	Cx43	Wnt/β-catenin	Inhibit the differentiation of osteoblasts	Up	Rabbit	[31]
mir-34a	In vivo and in vitro	mBMSCs, HUVECs, and rat	Runx2	—	BMSCs: Promote osteogenic differentiation and increase proliferation; HUVECs: acute inhibitory effect on angiogenesis in the early stage of steroid-induced ONFH, but it disturbed the normal vascular reparative process in the compensatory phase, which then indirectly aggravates ONFH.	Down in mBMSCs, and up in HUVECs	Human and rat	[32]
	In vivo	Rat serum	Tgif2	OPG/RANK/RANKL	Alleviate ONFH	Down	Rat	[33]
	In vitro and in vivo	mBMSCs and mice	CDK4, CDK6, and cyclin D1	JAG1/Notch	Inhibit BMSCs proliferation and osteoblastic differentiation	Up	Mice	[34]
miR-181d	In vitro	hBMSCs	Smad3	Smad3	Inhibit osteobalsitc differentiation of BMSCs	Up	Human	[35]
miR-200a	In vitro	Osteoblasts	Keap1/Nrf2	Nrf2	Protect osteoblasts from dex	Down	Human	[36]
miR-146a	In vitro	Murine osteoblasts	Bcl2	Bcl2	Inhibits proliferation and induce apoptosis	Up	Murine	[37]
	In vivo	Rabbit	Wnt	Wnt/β-catenin	Promote angiogenesis; inhibited the apoptosis of bone cells	Up	Rabbits	[38]
miR-145	In vivo and in vitro	Human THP-1 cells and rat	OPG	OPG/(RANKL)/RANK	Inhibit osteoclast differentiation and prevent excessive bone resorption	Down	Human and rat	[39]
miR-25-5p	In vitro	Osteoblasts	PKCζ	AMPK	Protect osteoblasts from steroid	Up	Human	[40]
miR-23a-3p	In vivo and in vitro	mBMSCs and rat	LRP5	—	Inhibit osteogenic differentiation	Up	Rat	[41]
miR-708	In vivo and in vitro	hBMSCs	Smad3	Smad3	Inhibit osteogenic differentiation and enhance adipogenesis differentiation	Up	Human	[20]
miR-210	In vivo and invitro	HUVECs and rat	—	—	activate the angiogenesis	Up	Human and rat	[18]
miR-135b	In vitro	Osteoblastic	Ppm1e	AMPK	Protects osteoblasts from steroid	Up	Human	[42]
mir-199a-5p	In vivo and intro	Osteoblasts and rat	Wnt	FZD4, WNT2	Inhibit cell proliferation in differentiating osteoblasts	Up	Human and rat	[43]
miR-548d-5p	In vitro	hBMSCs	PPARγ	PPARγ	Suppress steroid-induced adipogenic differentiation of and enhance osteogenic potential.	Down	Human	[44]
miR-17/20a	In vivo and vitro	Osteoblasts and rat	RANKL	RANKL	Inhibit steroid-induced osteoclast differentiation	Down	Human and rat	[45]

Note. miRNAs, microRNAs; ONFH, osteonecrosis of the femoral head; BMSCs, bone marrow mesenchymal stem cells; GREM1, gremlin 1; BMP, bone morphogenesis protein; EGFR, epidermal growth factor receptor; DKK1, dickkopf-related protein 1; TGF-β, transforming growth factor-β; PPARγ, peroxisome proliferator-activated receptor gamma; Runx2, Runt-related transcription factor 2; CYP1A2, cytochrome P450 1A2; PDCD4, programmed cell death protein 4; Cx43, Connexin43; HUVECs, human umbilical vein endothelial cells; Tgif2, transforming growth factor-beta-induced factor homeobox 2; OPG, osteoprotegerin; RANK, Receptor activator of nuclear factor B; RANKL, receptor activator of nuclear factor B ligand; Nrf2, NF-E2-related factor 2; Bcl2, B-cell lymphoma-2; PKCζ, protein kinase C ζ; AMPK, AMP-activated protein kinase; LRP-5, low-density lipoprotein receptor-related protein 5.