Long noncoding RNA H19 accelerates tenogenic differentiation and promotes tendon healing through targeting miR‐29b‐3p and activating TGF‐β1 signaling

Abstract

Tendon injures are common orthopedic conditions, but tendon development and the pathogenesis of tendon injures, such as tendinopathy, remain largely unknown and have limited the development of clinical therapy. Studies on tenogenic differentiation at the molecular level may help in developing novel therapeutic strategies. As novel regulators, long noncoding RNAs (lncRNAs) have been found to have widespread biological functions, and emerging evidence demonstrates that lncRNAs may play important regulatory roles in cell differentiation and tissue regeneration. In this study, we found that lncRNA H19 stimulated tenogenesis of human tendon-derived stem cells. Stable overexpression of H19 significantly accelerated TGF-β1-induced tenogenic differentiation and accelerated tendon healing in a mouse tendon defect model. H19 directly targeted miR-29b-3p, which is considered to be a negative regulator of tenogenesis. Furthermore, miR-29b-3p directly suppressed the expression of TGF-β1 and type I collagen, thereby forming a novel regulatory feedback loop between H19 and TGF-β1 to mediate tenogenic differentiation. Our study demonstrated that H19 promotes tenogenic differentiation both and by targeting miR-29b-3p and activating TGF-β1 signaling. Regulation of the TGF-β1/H19/miR-29b-3p regulatory loop may be a new strategy for treating tendon injury.-Lu, Y.-F., Liu, Y., Fu, W.-M., Xu, J., Wang, B., Sun, Y.-X., Wu, T.-Y., Xu, L.-L, Chan, K.-M., Zhang, J.-F., Li, G. Long noncoding RNA H19 accelerates tenogenic differentiation and promotes tendon healing through targeting miR-29b-3p and activating TGF-β1 signaling.

Silencing of lncRNA AK045490 Promotes Osteoblast Differentiation and Bone Formation via β-Catenin/TCF1/Runx2 Signaling Axis

“…In MC3T3-E1 cells, knockdown of AK045490 significantly increased the expression of osteoblast differentiation marker genes (Alp, Ocn, and Col Iα1), the ALP activity and the formation of mineralized nodules (Figure 2), which were consistent with the phenomenon that the elevated AK045490 expression in bone tissue was accompanied by deteriorated bone microstructure and decreased bone formation in aging mice, as well as in OVX mice. Several canonical signaling pathways, such as the TGF-beta signaling pathway [14][15][16], the MAPK signaling pathway [17], the Hippo signaling pathway [18], the Notch signaling pathway [19], the Jak-STAT signaling pathway, and the Toll-like receptor signaling pathway [12], which are associated with the osteoblast differentiation, have been found to be closely related to lncRNAs. All of these findings indicated that lncRNAs are critical elements in osteoblast differentiation.…”

Metformin Protects against Oxidative Stress Injury Induced by Ischemia/Reperfusion via Regulation of the lncRNA-H19/miR-148a-3p/Rock2 Axis

“…Interestingly, the function of lncRNA is usually mediated through the regulation of microRNAs that regulate mRNA expression by binding to the 3 ′ untranslated region (3 ′ UTR) after transcription [12]. For example, lncRNA-H19 negatively modifies cell differentiation by direct targeting of miR-29b-3p followed by inhibition of TGF-β1 COL1A1 expression [13]. Based on miRNA expression profiling in ischemic stroke, it has been shown that some miRNAs may be potential biomarkers for the diagnosis of stroke or prediction of prognosis.…”

Long non-coding RNA H19 deficiency ameliorates bleomycin-induced pulmonary inflammation and fibrosis

“…al., reported that H19 could enhance TGF-β signaling in both hepatic stellate cells and hepatocytes and facilitate liver brosis [47]. H19 was also showed to accelerate TGF-β1-induced tenogenic differentiation in vitro and promoted tendon healing in a mouse tendon defect model [48]. It thus suggests that H19 enhances the pulmonary brosis maybe partly via activation of TGF-β/smad signaling.…”