Role of long non-coding RNA H19 in the development of osteoporosis

Abstract

Background: Osteoporosis is a widespread and serious metabolic bone disease. At present, revealing the molecular mechanisms of osteoporosis and developing effective prevention and treatment methods are of great significance to health worldwide. LncRNA is a non-coding RNA peptide chain with more than 200 nucleotides. Researchers have identified many lncRNAs implicated in the development of diseases and lncRNA H19 is an example.

Results: A large amount of evidence supports the fact that long non-coding RNA (lncRNA) genes, such as H19, have multiple, far-reaching effects on various biological functions. It has been found that lncRNA H19 has a role in the regulation of different types of cells in the body including the osteoblasts, osteocytes, and osteoclasts found in bones. Therefore, it can be postulated that lncRNA H19 affects the incidence and development of osteoporosis.

Conclusion: The prospect of targeting lncRNA H19 in the treatment of osteoporosis is promising because of the effects that lncRNA H19 has on the process of osteogenic differentiation. In this review, we summarize the molecular pathways and mechanisms of lncRNA H19 in the pathogenesis of osteoporosis and summarize the research progress of targeting H19 as a treatment option. Research is emerging that explores more effective treatment possibilities for bone metabolism diseases using molecular targets.

Keywords: Long noncoding RNA; Osteogenesis; Osteoporosis; lncRNA H19.

Fig. 1

Mechanisms of action of lncRNAs in bone development. LncRNA regulates osteogenic differentiation through Wnt/β-catenin and MAPK pathways. lncRNA ANCR and lncRNA HOTAIR affect the Wnt/β-catenin pathway and inhibit osteogenic differentiation. LncRNA DANCR and LncRNA SNHG1 regulate osteogenic differentiation through the MAPK pathway. LncRNA regulates osteoclast differentiation through RANK/RANKL/OPG and other pathways. LncRNA Bmncr inhibits RANKL-induced osteoclast differentiation

Fig. 2

Mechanism of H19 regulating osteogenic differentiation. (1) H19 Promotes osteoblast differentiation via the TGF-β1/Smad3/HDAC signaling pathway by deriving miR-675. (2) H19 regulates the Notch signaling pathway by regulating downstream miRNA expression ligands to promote the osteogenic differentiation of MSCs induced by BMP9 (3) H19 is the miRNA sponge of miR141 and miR22, which antagonizes the negative regulatory effects of two miRNAs on the Wnt/βcatenin pathway. (4) H19 targets DKK4 to halt its inhibitory effect on the Wnt signaling pathway and osteogenic function. (5) miR-138 sponge reduces the expression of PTK2 gene by competitively binding with H19, promotes FAK expression, and induces osteogenic differentiation of MSCs. (6) H19 promotes the proliferation of osteoblasts by inhibiting the expression of p53. (7) The combination of H19 and Foxc2 synergistically promotes the osteogenic differentiation of bone marrow mesenchymal stem cells