Table 2.

Upregulated miRNAs during fracture healing and their significantly correlated mRNAs. Reported verified target mRNAs in human and rodent species for the 54 DE miRNAs (listed in Fig. 6) were searched in PubMed (data published by June 2020). Spearman correlation test in R was carried out between miRNA and target mRNA expression levels in individual samples. miRNAs that were downregulated compared to D0 bone and their target mRNA with negative correlation in the expression levels are listed here. No correlation was found between any of the published targets for upregulated 133b-3p, 181a-1-3p, and miR-497a-3p. No targets have been verified in the literature for miR-133b-3p, miR-434-5p, miR-5099 and miR-322-3p. Entire list of the validated target search, with references and correlation coefficient values between miRNAs and target mRNAs is presented in Supplemental File 5.

Upregulated miRNAs during fracture healing and their significantly correlated mRNAs. Reported verified target mRNAs in human and rodent species for the 54 DE miRNAs (listed in Fig. 6) were searched in PubMed (data published by June 2020). Spearman correlation test in R was carried out between miRNA and target mRNA expression levels in individual samples. miRNAs that were downregulated compared to D0 bone and their target mRNA with negative correlation in the expression levels are listed here. No correlation was found between any of the published targets for upregulated 133b-3p, 181a-1-3p, and miR-497a-3p. No targets have been verified in the literature for miR-133b-3p, miR-434-5p, miR-5099 and miR-322-3p. Entire list of the validated target search, with references and correlation coefficient values between miRNAs and target mRNAs is presented in Supplemental File 5.

Cluster	miRNA	Targets with negative correlation	Targets with positive correlation
	28 upregulated miRNAs ↔ 105 negatively correlating and 107 positively correlating mRNAs
D5	miR-136-3pa	Pten
D5	miR-410-3pa	Cxcr5, Fmr1, Yy1, Pten	Stat3, Tgfbr2, Snai1
D5	miR-411-5pa	Txnip, Vasp, Grb2
D5	miR-434-3pa	Eif5a1
D5	miR-541-5pa	Cdk6
D5	miR-133a-3p	Met
D5	miR-381-3p	Ube2c, Cdk6, Map3k8, Cxcr4	Ets2, Fgf7, Lrp6
D7	miR-127-3pa	Kif3b	Bag5
D7	miR-99b-5p		Fzd8
D7	miR-152-3p	Atg12, Fasl, Brd4, Dnmt1	Klf4, Slc2a1, Foxf1a, Klf4
D7	miR-214-3p	Nlrc5, Hmga1, St6gal1, Atg12, Ezh2, Ezh1, Pim1, Stat6, Cadm1, Pten	Ctnnb1, Pdk1, Abcb1, C1qtnf9, Irs1, Runx3, Foxp2, Mmp2, Plcb1, Ctrp9, Pdk1
D7	miR-335-3p	Kdm4c, Plaur
D7	miR-351-5p	Mapk13	Sirt6
D7	miR-450b-5p		Yap1, Kif26b
D10	miR-140-3pa	Cxcl12, Trpm2, Cd38, Tnfa, Jak1, Sirt1, Atp1b, Myb, Mcf2l, Atp8a1, Bcl2	Klf4, Pthlh, Masp1, Acan, Col4a1, Pycr1, Tgfb3, Trps1
D10	miR-140-5pa	Tnf, Nfe2l2, Map3k11, Stat1, Bloc1s2, Creb1, Birc5, Glul, Hdac4, Pin1, Adam10, Igf1r, Hmgb1, Hmgn5, Tlr4	Vegfa, Sept2, Pak4, Six1, Smurf1, Meg3, Plod1, Sox4, Thy1, Ndrg3, Frs2, Sox9, Cemip, Fgfrl1, Muc1, Runx3, Hoxa11, Snai2, Pdgfra, Smad3, Yes1, Foxo1, Zeb1
D10	miR-455-3pa	Fam83f	Runx2, Dusp3, Zeb1
D10	miR-455-5pa	Lgals9, Jak1, Myd88, Dnmt1, Kdm6b	Rab31, S1pr1, Socs3, Runx2, Rab18
D10	miR-34c-5p	Gucy1b3, Flot2, Sp1, Etv6, Atg4b, Ccl22, Gucy1b3	Bmf
D10	miR-214-5p	Rock1, Klf5, Cxcr5, E2f2, Ciz1	Wasl, Dpysl5, Tm4sf1, Col4a1
D14	miR-148a-3pa	Dnmt1, Ikbkb, Mcl1, Kdm6b, Snhg4	Runx3
D14	miR-182-5pa	Rab27a, Flot1, Foxo3, Cdkn1b, Bcl2l12, Sesn2, Cfl1, Creb1, Pten	Bnip3, Igf1, Pthlh, Reck, Smad4, Cd2ap, Hoxa9, Rnd3, Gli2, Dll4, Efnb1
D14	miR-99a-5p		Hoxa1
D14	miR-148a-5p		Serpinh1, Tlr3
D14	miR-152-5p	Txnip	Smad3, Fbxl7, Pik3ca
D14	miR-199a-5p	Ccr7, Mst1, Ccnb1, Slit1, Nfkb1, Rela, Ccn2, Rock1, March8, Fkbp5, Sirt1	Fzd6, Hif1a, Zeb1, Osgin2, Tgfb2, Pik3ca, Ece1, Pias3, Pvrl1, Srgap2, Vegfa, Arhgap12, Map4k3, Mafb
D14	miR-322-5p	Fam3b, Nfkb1
D14	miR-335-5p		Ldhb, Bcl2l2, Dancr, Aplnr, Tnfsf11

^aCartilage-associated DE miRNA, see Fig. 4.