4.4 Article

RUNX3 derived hsa_circ_0005752 accelerates the osteogenic differentiation of adipose-derived stem cells via the miR-496/MDM2-p53 pathway

Journal

REGENERATIVE THERAPY
Volume 18, Issue -, Pages 430-440

Publisher

ELSEVIER
DOI: 10.1016/j.reth.2021.09.006

Keywords

RUNX3; Adipose-derived stem cells; Osteogenic differentiation; Circular RNAs; microRNA; MDM2

Funding

  1. Hunan Provincial Health Commission [C2019108]

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This study revealed that RUNX3 promotes osteogenic differentiation by regulating the hsa_circ_0005752/miR-496/MDM2 axis, offering a new therapeutic strategy for osteoporosis.
Background: Circular RNAs (circRNAs) are non-coding RNAs that play a pivotal role in bone diseases. RUNX3 was an essential transcriptional regulator during osteogenesis. However, it is unknown whether RUNX3 regulates hsa_circ_0005752 during osteogenic differentiation. Methods: The levels of hsa_circ_0005752 and RUNX3 were measured by qRT-PCR after osteogenic differentiation of ADSCs. The osteogenic differentiation was analyzed by Alkaline phosphatase (ALP) staining and Alizarin red staining (ARS). qRT-PCR and western blot were used to assess the expressions of osteogenic differentiation-related molecules. RNA pull-down, RIP, and luciferase reporter assays determine the interactions between miR-496 and hsa_circ_0005752 or MDM2 mRNA. CHIP-PCR analyzed the interaction between RUNX3 and LPAR1. Finally, the potential roles of RUNX3 were investigated during osteogenic differentiation with or without hsa_circ_0005752 knockdown. Results: Hsa_circ_0005752 and RUNX3 were significantly increased, and miR-496 was remarkably decreased in ADSCs after osteogenic differentiation. Hsa_circ_0005752 could promote osteogenic differentiation, as shown by enhancing ALP and ARS staining intensity. Hsa_circ_0005752 enhanced the expressions of Runx2, ALP, Osx, and OCN. Furthermore, hsa_circ_0005752 directly targeted miR-496, which can directly bind to MDM2. RUNX3 bound to the LPAR1 promoter and enhanced hsa_circ_0005752 expressions. Moreover, the enhanced expression of hsa_circ_0005752 by RUNX3 could promote osteogenic differentiation, whereas knockdown of hsa_circ_0005752 partially antagonized the effects of RUNX3. Conclusion: Our study demonstrated that RUNX3 promoted osteogenic differentiation via regulating the hsa_circ_0005752/miR-496/MDM2 axis and thus provided a new therapeutic strategy for osteoporosis. (C) 2021, The Japanese Society for Regenerative Medicine. Production and hosting by Elsevier B.V.

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