Author Correction: miR-21 deficiency inhibits osteoclast function and prevents bone loss in mice

Correction to: Scientific Reports 10.1038/srep43191, published online 27 February 2017

This Article contains errors in Figure 5 and Figure 7.

In Figure 5i in the “M, miR-21^−/− + PDCD4” group shows partial overlap with Figure 5e, the “M, WT” group. The corrected Figure 5 and its accompanying legend appears below.

Figure 5.

miR-21 promotes bone resorption in vivo and controls osteoclastogenesis by targeting programmed cell death 4 (PDCD4). (a) Tartrate resistant acid phosphotase (TRAP) staining of the trabecular bone in histological sections of 3-month WT and miR-21^−/− mice. Tibiae were decalcified, embedded in paraffin, sectioned, and stained for TRAP. Bars: 25 μm. (b,c) Corresponding parameters showed inhibited osteoclastogenesis and bone resorption in miR-21^−/− mice. N.Oc/BS, number of osteoclasts per bone surface (b). Oc.S/BS, osteoclast surface per bone surface (c). (d) Enzyme-linked immunosorbent assay (ELISA) detection of the serum bone resorption marker of 3-month WT and miR-21^−/− mice. miR-21 deficiency inhibited the bone resorption rate. CTX-1, cross linked C-telopeptide of type 1 collagen. (e,f) Representative images (e) and the corresponding parameter (f) demonstrated that miR-21^−/− osteoclasts (OCs) generated declined resorption pits on dentine slices. Resorption pits were stained with toluidine blue. M, macrophage colony-stimulating factor (M-CSF). RL, receptor activator of nuclear factor κB ligand (RANKL). Tt.Ar, total area. Bars: 100 μm. (g) Western blot analysis of mature OCs derived from 3-month WT and miR-21^−/− mice. OCs were differentiated with M-CSF and RANKL. miR-21 deficiency promoted the PDCD4 protein level, a functional target of miR-21, which suppressed the phosphorylation level of c-fos. Cropped blots are displayed with only brightness adjusted equally across the entire images. (h) Quantitative real-time polymerase chain reaction (qRT-PCR) analysis of miR-21^−/− mature OCs demonstrated down-regulation of mRNA level of PDCD4 by small interfering RNA. OCs were differentiated with M-CSF and RANKL. siPDCD4, small interfering RNA for PDCD4. NC, negative control of siPDCD4. (i,j) Representative images (i) and the corresponding parameter (j) demonstrated that down-regulation of PDCD4 rescued resorption capability of miR-21^−/− OCs on dentine slices. Resorption pits were stained with toluidine blue. Bars: 100 μm. Data represents mean ± standard errors of the mean. n = 6/genotype (a–g), n = 3/group (h) and n = 4/group (i,j). Statistical significance was evaluated by two-tailed Student’s t test for two-group comparison, and one way analysis of variation (ANOVA) with Newman-Keuls post-hoc tests for multiple comparisons. *P < 0.05. NS, not significant (P > 0.05).

Additionally, in Figure 7d, the “WT, aged” group overlaps with Figure 6d, the “WT, OVX” group. The corrected Figure 7, and its accompanying legend appears below.

Figure 7.

miR-21 contributes to age-related osteopenia and bone loss in human. (a) Representative micro-CT images demonstrating bone phenotypes of 16-month WT and miR-21^−/− mice. Orange frames indicate the region of interest analyzed for trabecular bone mass in the distal femoral metaphysis (up). Cortical bone mass was analyzed in the midshaft of femora (bottom). Bars: 500 μm. (b,c) Corresponding parameters showed that miR-21 deficiency prevented age-related trabecular (b) and cortical (c) bone loss. BV/TV, bone volume per tissue volume. Ct.Th, cortical thickness. (d) Tartrate resistant acid phosphotase (TRAP) staining of the trabecular bone of 16-month WT and miR-21^−/− mice. Tibiae were decalcified, embedded in paraffin, sectioned, and stained for TRAP. Bars: 25 μm. (e,f) The corresponding parameter of TRAP and the serum bone resorption marker detected by enzyme-linked immunosorbent assay (ELISA) showed that miR-21 deficiency blocked age-related osteoclastogenesis and bone resorption. Oc.S/BS, osteoclast surface per bone surface (e). CTX-1, cross linked C-telopeptide of type 1 collagen (f). (g) ELISA detection of serum ratio of receptor activator of nuclear factor κB ligand (RANKL) over osteoprotegerin (OPG). No significant difference was detected between 16-month WT and miR-21^−/− mice. (h) Quantitative real-time polymerase chain reaction (qRT-PCR) analysis demonstrated up-regulated mRNA level of miR-21 in serum of osteoporotic mice. N, normal. OP, osteopenia induced by ovariectomy (OVX). The above data represents mean ± standard errors of the mean. n = 6 per group of mice. Statistical significance was evaluated by two-tailed Student’s t test for two-group comparison, and by one way analysis of variation (ANOVA) followed by Newman-Keuls post-hoc tests for multiple comparisons. *P < 0.05. NS, not significant (P > 0.05). (i) In osteoporotic human samples, qRT-PCR analysis also detected up-regulated mRNA level of miR-21 in serum. N, healthy donor. OP, donor with postmenopausal osteoporosis. n = 9 per group. Results are given as box plots showing 5th, 50th and 95th percentiles, and minimum to maximum ranges. Two-tailed Mann–Whitney U test was used to determine the significance. *P < 0.05. (j) Bone mineral density (BMD) was inversely correlated with miR-21 in human serum. Pearson’s correlation: − 0.5679; p = 0.0140.