Table 1.

Summary of preclinical investigations on miRNAs-mediated targeting therapeutics in bone-related disorders.

Disorders	miRNA	Delivery system	Regulation	Gene of interest	In vitro/In vivo	Outcome summary	Reference
Osteoporosis (OP)	mmu-miR-17/20a-5p	Lipofectamine 2000 complexes	↑	RANKL	MC3T3-E1, C57BL/6 mice	窗体顶端	(Shi et al., 2014)
						Attenuated Dexamethasone- induced osteoclast differentiation and function
	mmu-miR-29a-3p	Lentivirus	↑	Dkk-1	SD rat	Protects against GC-induced bone loss and fragility	(Wang et al., 2013b)
	mmu-miR-34a-5p	X-tremeGENE Transfection Reagent	↓	CDK4, CDK6,	C57BL/6 mice	窗体顶端	(Kang et al., 2016a)
				Cyclin D1		Impaired BMSC osteogenic differentiation and aggravated osteoporsis
	mmu-miR-140/214-3p	Baculovirus vectors	↓	JAG1, Tmem119, ATF-4, Osterix	SD rat	Promoted bone formation and mitigated excessive bone resorption	(Li et al., 2016c)
	mmu-miR-34a-5p	Lipofectamine RNAi MAX	↑	Tgif2	C57BL/6J mice	Elevated bone resorption and reduced bone mass	(Krzeszinski et al., 2014)
Bone defect	hsa-miR-21-5p	Chitosan/hyaluronic acid nanoparticles	↑	Runx2	hBMSC	Significantly improved osteogenesis	(Schoolmeesters et al., 2009, Wang et al., 2015b)
	mmu-miR-26a-5p	Lipofectamine 2000 complexes	↑	OCN, COL1	窗体顶端	Satisfactory bone repair in tibial defect	(Wang et al., 2015a)
					Rabbit ASC
	mmu-miR-29a-3p	Gelatin solutions	↓	IGF1, tfgb1	MC3T3-E1	Significantly enhanced ECM deposition	(James et al., 2014)
	mmu-miR-31-5p	Lipofectamine 2000 complexes	↓	Runx2, Satb2	SD rat	Good biocompatibility and bone regeneration	(Deng et al., 2014, Deng et al., 2013)
	mmu-miR-138-5p	Lipofectamine 2000 complexes	↓	Runx2	C57BL/6 mice,	窗体顶端	(Yan et al., 2014)
					rat BMSC	Massive bone with good vascularization
	hsa-miR-148b-3p	Silver nanoparticle complexes	↑	Runx2, OCN	hASC	Promoted osteogenic differentiation	(Qureshi et al., 2013)
Primary bone tumor	hsa-miR-20a-5p	Lipofectamine 2000 complexes	↓	EGR	MG63, SaSO2, SW1353	Inhibited cell proliferation and cycle	(Zhou et al., 2015)
	hsa-miR-22-3p	Lipofectamine 2000 complexes	↑	ACLY	SaSO2, PC3, Hela, A549	Inhibited growth and metastasis of various tumors	(Xin et al., 2016)
	hsa-miR-26a-5p	Lentivirus vector	↑	Jagged1	MG63, SaSO2, 143B, U2OS, BALA/c nude mice	Suppressed CSCs phenotype and tumor growth	(Lu et al., 2016)
	hsa-miR-106a-5p	Lipofectamine 2000 complexes	↑	HMGA2	MG63, SaSO2, HOS, U2OS	Inhibited proliferation, migration and invasion	(He et al., 2016)
	hsa-miR-106b-5p	FuGENE HD transfection agent	↑	RANKL, IL-8, MMP2, TWIST	mice BMM, GCTSC, OVX mouse	Inhibited bone resorption and osteolysis	(Wang et al., 2015c)
	hsa-miR-126-5p	FuGENE HD transfection agent	↑	MMP-13, PTHrP	mice BMM, GCTSC	Suppression of osteoclast differentiation and bone resorption	(Wu et al., 2014a, Zhou et al., 2014)
	hsa-miR-126-5p	Lipofectamine 2000 complexes	↑	Sirt 1	SaSO2	窗体顶端	(Shi et al., 2015, Xu et al., 2013)
						inhibited proliferation, migration, invasion and epithelial-mesenchymal transition
	hsa-miR-204-5p
	hsa-miR-145-5p	Lipofectamine 3000 complexes	↓	FLI-1	MG63, SaSO2	Inhibited tumor progression	(Wu et al., 2016b)
	hsa-miR-409-3p	Lipofectamine 2000 complexes	↑	Catenin-δ1	U2OS	Inhibited migration and invasion	(Wu et al., 2016a)
	hsa-miR-646	Lipofectamine 2000 complexes	↑	FGF-2	MG63, SaSO2, HOS, U2OS	Suppression of metastasis	(Sun et al., 2015)
Secondary metastasis	hsa-miR-34a-5p	Lentivirus vector	↑	TCF-7	PC3, RasB1	Inhibited bone metastasis of Ras-activated PC	(Chen et al., 2015)
	hsa-miR-335-5p,	Lentivirus vector	↑	eNOS	PC3	Inhibited bone metastasis of PC	(Fu et al., 2015)
	hsa-miR-543
Osteoarthritis (OA)	hsa-miR-23a-3p,	Lipofectamine 2000 complexes	↓	Samd3	SW1353	Promoted type II collagen and aggrecan expression	(Kang et al., 2016b, Li et al., 2015)
	hsa-miR-16-5p
	hsa-miR-139-5p	Lipofectamine RNAi MAX	↓	EIF4G2, IGF1R	CHON-001	Protective effects on chondrocyte proliferation and migration	(Hu et al., 2016)
	hsa-miR-142-3p	Lipofectamine 2000 complexes	↑	HMGB-1	C57BL/6 mice	Suppressed inflammation and chondrocyte apoptosis	(Wang et al., 2016b)
	mmu-miR-210-5p	Geneporter 2 Transfection Reagent	↑	DR6	SD rat	Suppressed inflammation and chondrocyte apoptosis	(Zhang et al., 2015a)
	hsa-miR-365a-3p	Lipofectamine 2000 complexes	↓	HDAC4	Primary chondrocyte from OA patient	Inhibited expression of MMP13 and Col X	(Yang et al., 2016)