A novel PDIA3/FTO/USP20 positive feedback regulatory loop induces osteogenic differentiation of preosteoblast in osteoporosis

In this study, m6 A RNA methylation was detected by methylated RNA immunoprecipitation (MeRIP), while mRNA stability was identified by RNA decay assay. Besides, protein-protein interaction and protein phosphorylation were determined using co-immunoprecipitation (Co-IP). Herein, results revealed that PDIA3 promoted osteogenic differentiation of preosteoblast MC3T3-E1. Besides, PDIA3 mRNA methylation was suppressed by FTO alpha-ketoglutarate dependent dioxygenase (FTO) as RNA methylation reduced PDIA3 mRNA stability during osteogenic differentiation of MC3T3-E1 cells. Moreover, ubiquitin specific peptidase 20 (USP20) improved FTO level through inhibiting FTO degradation while PDIA3 increased FTO level by enhancing USP20 phosphorylation during osteogenic differentiation of MC3T3-E1 cells, suggesting a positive feedback regulatory loop between PDIA3 and FTO. In summary, these findings indicated the mechanism of PDIA3 regulating osteogenic differentiation of preosteoblast and provided potential therapeutic targets for osteoporosis.PMID:38321831 | DOI:10.1002/cbin.12134
Source: Cell Biology International - Category: Cytology Authors: Source Type: research