LncRNA ODIR1 inhibits osteogenic differentiation of hUC-MSCs through the FBXO25/H2BK120ub/H3K4me3/OSX axis

Abstract

Long noncoding RNAs (lncRNAs) have been demonstrated to be important regulators during the osteogenic differentiation of mesenchymal stem cells (MSCs). We analyzed the lncRNA expression profile during osteogenic differentiation of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) and identified a significantly downregulated lncRNA RP11-527N22.2, named osteogenic differentiation inhibitory lncRNA 1, ODIR1. In hUC-MSCs, ODIR1 knockdown significantly promoted osteogenic differentiation, whereas overexpression inhibited osteogenic differentiation in vitro and in vivo. Mechanistically, ODIR1 interacts with F-box protein 25 (FBXO25) and facilitates the proteasome-dependent degradation of FBXO25 by recruiting Cullin 3 (CUL3). FBXO25 increases the mono-ubiquitination of H2BK120 (H2BK120ub) which subsequently promotes the trimethylation of H3K4 (H3K4me3). Both H2BK120ub and H3K4me3 form a loose chromatin structure, inducing the transcription of the key transcription factor osterix (OSX) and increasing the expression of the downstream osteoblast markers, osteocalcin (OCN), osteopontin (OPN), and alkaline phosphatase (ALP). In summary, ODIR1 acts as a key negative regulator during the osteogenic differentiation of hUC-MSCs through the FBXO25/H2BK120ub/H3K4me3/OSX axis, which may provide a novel understanding of lncRNAs that regulate the osteogenesis of MSCs and a potential therapeutic strategy for the regeneration of bone defects.

Linc02349 promotes osteogenesis of human umbilical cord‐derived stem cells by acting as a competing endogenous RNA for miR‐25‐3p and miR‐33b‐5p

“…In our previous study, to identify functional lncRNAs correlating with osteogenesis, lncRNA microarrays were applied to analyse lncRNA expression profiles 22 . We revealed that 20 lncRNAs were upregulated and 9 were downregulated.…”

“…In our previous study, we identified lncRNA profile during the osteogenic differentiation induction of hUC‐MSCs using Agilent Human lncRNA Microarray. A total of 23 lncRNA were significantly differentially expressed upon osteogenic differentiation 22 . Among those, LOC100506530 (the alternative name of linc02349) was significantly increased.…”

Selective laser melted Fe-Mn bone scaffold: microstructure, corrosion behavior and cell response

“…In present study, micro scale pores and ravines was built on the strut connection sites, which provided superior appearance environment for cells proliferation and adhesion on the scaffolds. Besides, the porous structure also provided diversified mechanical stimuli for adhered cells, thus might enhance the osteoblast differentiation [54,55]. In short, in vitro assays revealed the good cytocompatibility of SLM derived Fe-25Mn scaffold.…”

In situ decomposition of Ti2AlN promoted interfacial bonding in ZnAl-Ti2AlN biocomposites for bone repair

“…In terms of biocompatibility, as an abundant element in the human body, Zn plays a vital role in cell proliferation and the metabolism of human body [6][7][8][9]. As for biodegradability, it was reported that Zn alloys exhibited moderate degradation rate that could meet the requirements for bone repair [10][11][12][13][14]. What's more, the degradation products show good biocompatibility [15].…”