Involvement of Noncoding RNAs in the Differentiation of Osteoclasts

Table 1

Major ncRNAs related to biological events in osteoclasts.

miRNA (miR)	Validated target(s)	Functions	Expression	Effect(s)	References
lncRNA-LINC00311	DLL3	Positive	Not mentioned	Promotes osteoclast proliferation and differentiation, shifts cell cycle distribution, and inhibits apoptosis	[101]
lncRNA-AK077216	Not mentioned	Positive	Upregulated	Inhibits OCP apoptosis and promotes osteoclast differentiation, fusion, bone-resorbing activity, and actin ring formation	[98]
lncRNA-CRNDE	Not mentioned	Positive	Not mentioned	Promotes osteoclast proliferation and shifts cell cycle distribution	[113]
lncRNA-MAYA	Not mentioned	Positive	Not mentioned	Promotes osteoclast differentiation and bone-resorbing activity	[136]
lncRNA-MIRG	Not mentioned	Positive	Upregulated	MIRG inhibition decreases osteoclast differentiation and bone-resorbing activity	[83]
lncRNA-MALAT1	Not mentioned	Positive	Not mentioned	EPC-derived exosomal MALAT1 promotes osteoclast differentiation and migration	[82]
lncRNA-DANCR	Not mentioned	Positive	Not mentioned	Knockdown of DANCR reduces the promotion effect of compression force on osteoclastogenesis	[104, 105]
lncRNA-TUG1	Not mentioned	Positive	Not mentioned	Promotes osteoclast proliferation and inhibits osteoclast apoptosis	[112]
lncRNA-Jak3	Not mentioned	Positive	Upregulated	Regulates the Jak3-NFATc1-CTSK axis; lncRNA-Jak3 knockdown inhibits osteoclast differentiation and bone-resorbing activity	[100]
circRNA_28313	Not mentioned	Positive	Upregulated	circRNA_28313 knockdown inhibits osteoclastogenesis and actin ring formation	[29]
miR-21	PDCD4, FasL	Positive	Upregulated	Downregulates PDCD4 and forms a c-Fos/miR-21/PDCD4 positive feedback loop and promotes osteoclast differentiation and bone-resorbing activity while inhibiting apoptosis	[23, 26, 78, 117, 163, 164, 185, 188–191]
miR-29	NFI-A, CALCR, CDC42, SRGAP2, GPR85, CD93	Positive	Upregulated	Promotes osteoclast differentiation, survival, and bone-resorbing activity	[78, 117, 129, 190, 191]
miR-214	PTEN	Positive	Upregulated	Downregulates PTEN and regulates the PTEN-PI3K-AKT axis, promotes osteoclast activity, and mediates osteoclast-osteoblast intercellular crosstalk	[108, 109, 117, 190, 192]
miR-182	PKR	Positive	Upregulated	Downregulates PKR, promotes osteoclast differentiation and bone-resorbing activity	[88, 115]
miR-183	HO-1	Positive	Upregulated	Downregulates HO-1, promotes osteoclastogenesis	[117, 118, 190]
miR-31	RhoA	Positive	Upregulated	Negatively regulates RhoA expression at an appropriate level; miR-31 inhibition inhibits osteoclast formation, bone-resorbing activity, and actin ring formation	[78, 117, 139, 191]
miR-34c	LGR4	Positive	Upregulated	Downregulates LGR4, promotes the formation of actin rings and TRAP-positive multinucleated cells	[97]
miR-148a	MAFB	Positive	Upregulated	Downregulates MAFB, promotes osteoclastogenesis	[78, 117, 123, 124, 190]
miR-9718	PIAS3	Positive	Unregulated	Downregulates PIAS3, promotes osteoclastogenesis	[117, 126, 127, 190]
miR-483-5p	IGF2	Positive	Not mentioned	Downregulates IGF2, promotes osteoclast differentiation and survival	[71]
miR-506	SIRT1	Positive	Upregulated	Downregulates SIRT1; a miR-506 inhibitor suppresses osteoclastogenesis	[128]
miR-363-3p	PTEN	Positive	Upregulated	Targets PTEN to activate the PI3K/AKT signaling pathway, promotes osteoclastogenesis	[110]
miR-125a-5p	TNFRSF1B	Positive	Upregulated	Downregulates TNFRSF1B, promotes osteoclastogenesis, OCP proliferation, and growth, migration, and invasion of RAW264.7 cells	[66]
miR-142-5p	PTEN	Positive	Upregulated	Targets PTEN to activate the PI3K/AKT signaling pathway, promotes osteoclast differentiation and activity	[111]
miR-199a-5p	MAFB	Positive	Upregulated	Suppresses MAFB, promotes osteoclast differentiation	[125]
miR-145-5p	OPG	Positive	Not mentioned	Suppresses OPG, promotes osteoclastogenesis	[49]
miR-212	IL-15, CX3CR1	Positive	Upregulated	Downregulates IL-15; miR-212 inhibition impairs osteoclastogenesis	[33]
miR-132	IRF1	Positive	Upregulated	Downregulates IRF1; miR-132 inhibition impairs osteoclastogenesis	[33]
miR-99b	IGF1R	Positive	Upregulated	Downregulates IGF1R; miR-99b inhibition impairs osteoclastogenesis	[33]
miR-let-7e	TNFAIP3, ITGA4, THBS1	Positive	Upregulated	Downregulates TNFAIP3, ITGA4, and THBS1; miR-let-7e inhibition impairs osteoclastogenesis	[33]
miR-146a-5p	Not mentioned	Positive	Not mentioned	miR-146a-5p knockdown impairs osteoclast differentiation and bone resorption	[172]
lncRNA-NONMMUT037835.2	Not mentioned	Negative	Downregulated	Inhibits osteoclastogenesis	[40]
lncRNA-Bmncr	Not mentioned	Negative	Downregulated	Inhibits osteoclast differentiation and bone-resorbing activity	[171]
miR-218	TNFR1, TLR4, MMP9	Negative	Downregulated	Inhibits the p38MAPK-c-Fos-NFATc1 pathway, represses TNFR1, TLR4, and MMP9, inhibits osteoclastogenesis, cell migration, actin ring formation, and bone resorption	[58, 73, 86, 117, 158, 190]
miR-34a	Tgif2	Negative	Downregulated	Downregulates Tgif2, inhibits osteoclast differentiation and bone-resorbing activity	[117, 120, 190, 191]
miR-155	MITF, Socs1	Negative	Downregulated	Downregulates MITF, PU.1, and Socs1, inhibits osteoclast fusion, differentiation, and bone-resorbing activity	[23, 31, 78, 89, 90, 190, 191]
miR-7b	DC-STAMP	Negative	Downregulated	Downregulates DC-STAMP, inhibits osteoclast differentiation and bone-resorbing activity	[117, 132]
miR-26a	CTGF	Negative	Upregulated	Downregulates CTGF; inhibits osteoclastogenesis, actin ring formation, and bone-resorbing activity	[117, 134, 190]
miR-124	NFATc1, Rab27a, IL-11	Negative	Downregulated	Downregulates NFATc1, Rab27a, and IL-11, inhibits the proliferation and motility of OCPs, and decreases osteoclast differentiation and activity	[37, 78, 80, 117, 166, 167, 190, 191]
miR-125a	TRAF6, TNFAIP3	Negative/positive	Downregulated/upregulated	Inhibited by NFATc1; inhibits osteoclast differentiation and downregulates TRAF6; miR-125a inhibition suppresses osteoclastogenesis and upregulates TNFAIP3	[33, 57, 78, 117, 190, 191]
miR-146a	TRAF6	Negative	Downregulated/upregulated	Downregulates TRAF6, inhibits osteoclastogenesis	[56, 77, 78, 117, 190, 191, 193, 194]
miR-503	RANK	Negative	Not mentioned	Downregulates RANK, inhibits osteoclast differentiation and bone-resorbing activity	[38, 78, 117, 190, 195]
miR-145	Smad3	Negative	Downregulated	Downregulates Smad3, inhibits osteoclast differentiation and bone-resorbing activity	[60]
miR-142-3p	PKCα	Negative	Downregulated	Downregulates PKCα, inhibits osteoclast clustering, fusion, differentiation, and survival	[141]
miR-222-3p	Potential: c-Src	Negative	Downregulated	Negatively regulates c-Src, inhibits osteoclast differentiation and bone-resorbing activity	[137]
miR-340	MITF	Negative	Downregulated	Downregulates MITF, inhibits osteoclastogenesis	[121, 185]
miR-16-5p	Not mentioned	Negative	Downregulated	Inhibits osteoclastogenesis and disrupts the structure of F-actin rings	[170]
miR-126-5p	MMP13	Negative	Not mentioned	Downregulates MMP13, inhibits osteoclast differentiation and bone-resorbing activity	[159, 160]
miR-17	PTP, Vav3 (potential)	Negative	Not mentioned	miR17/PTP/EphA4 regulatory axis: decreased miR-17 upregulates PTP, PTP downregulates EphA4, which activates osteoclastogenesis; may downregulate Vav3 and thus inhibits osteoclast fusion	[140, 155, 196]
miR-141	MITF, CALCR, EphA2	Negative	Downregulated	Downregulates MITF, CALCR, and EphA2; inhibits osteoclast differentiation and activity	[52, 55]
miR-219	MITF, TRAF6	Negative	Downregulated	Downregulates MITF and TRAF6, inhibits osteoclast differentiation and activity	[55]
miR-190	CALCR	Negative	Downregulated	Downregulates CALCR, inhibits osteoclast differentiation and activity	[55]
miR-23a	GSK3-β	Negative	Downregulated	Inhibits GSK3-β activation, inhibits osteoclast differentiation and activity	[95]
miR-1225	Keap1	Negative	Downregulated	Downregulates Keap1, inhibits osteoclast differentiation and activity	[119]
miR-100-5p	FGF21	Negative	Downregulated	Downregulates FGF21, inhibits osteoclastogenesis	[50]
miR-27a	PPARγ, APC	Negative	Not mentioned	Downregulates PPARγ and APC, inhibits osteoclast differentiation and activity in physiologic condition and ovariectomized (OVX) mice	[84]
miR-618	TLR4	Negative	Downregulated	Inhibits osteoclastogenesis via the TLR4/MyD88/NF-κB signaling pathway	[73]
miR-30a	DC-STAMP	Negative	Downregulated	Downregulates DC-STAMP, inhibits osteoclast formation, differentiation, and activity	[133]
miR-144-3p	RANK	Negative	Downregulated	Downregulates RANK, inhibits osteoclast differentiation, formation, proliferation, and apoptosis	[39]
miR-9	Cbl	Negative	Not mentioned	Downregulates Cbl, inhibits osteoclast survival and OCP migration	[153]
miR-181a	Cbl	Negative	Not mentioned	Downregulates Cbl, inhibits osteoclast survival and OCP migration	[153]
miR-29b	BMF	Negative/positive	Upregulated/downregulated	Downregulates BMF; knockdown impairs osteoclast migration, commitment, and formation; inhibits osteoclast differentiation and activity; enhances osteoclast survival	[122, 129, 147]
miR-378	Not mentioned	Negative/positive	Upregulated	Overexpression and underexpression of miR-378 inhibit osteoclastogenesis	[55, 76–78]
miR-223	NFI-A, IKKα (potential)	Negative/positive	Downregulated	Promotes osteoclastogenesis by regulating the relative expression of NFI-A and CSF1R, downregulates IKKα, and inhibits osteoclastogenesis	[25, 27, 64, 77, 78, 117, 148, 150, 190]
miR-133a	MITF, MMP14, CXCL11, CXCR3, SLC39A1	Negative/positive	Upregulated	Downregulates MITF, MMP14, CXCL11, CXCR3, and SLC39A1; both positive and negative effects on osteoclastogenesis are reported	[55, 75, 78, 92, 117, 197]
miR-106b	RANKL	Negative/positive	Not mentioned	Downregulates RANKL, has different regulatory roles in CIA bone microenvironment and giant cell tumor of bone	[41, 43]
miR-422a	Potential: Cbl, CD226, IGF1, CBP, TOB2	Positive	Upregulated	Unclear (probably inhibits those five inhibitors of osteoclastogenesis)	[47, 78, 117]
miR-338-3p	IKKβ, MAFB, RANKL	Negative/positive	Upregulated/downregulated	Downregulates IKKβ, MAFB, and RANKL; both positive and negative effects on osteoclastogenesis are reported	[42, 44, 62]