Open AccessCircFOXP1/FOXP1 promotes osteogenic differentiation in adipose‐derived mesenchymal stem cells and bone regeneration in osteoporosis via miR‐33a‐5p
Author(s) -
Shen Wanxiang,
Sun Bin,
Zhou Chenghong,
Ming Wenyi,
Zhang Shaohua,
Wu Xudong
Publication year - 2020
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.15792
Subject(s) - mesenchymal stem cell , microrna , microbiology and biotechnology , stem cell , adipose tissue , chemistry , bone healing , regeneration (biology) , osteoporosis , biology , endocrinology , anatomy , biochemistry , gene
Osteoporosis (OP) is defined by bone mass loss and structural bone deterioration. Currently, there are no effective therapies for OP treatment. Circular RNAs (circRNAs) have been reported to have an important function in stem cell osteogenesis and to be associated with OP. Most circRNA roles in OP remain unclear. In the present study, we employed circRNA microarray to investigate circRNA expression patterns in OP and non‐OP patient bone tissues. The circRNA‐miRNA‐mRNA interaction was predicted using bioinformatic analysis and confirmed by RNA FISH, RIP and dual‐luciferase reporter assays. ARS and ALP staining was used to detect the degree of osteogenic differentiation in human adipose‐derived mesenchymal stem cells (hASCs) in vitro. In vivo osteogenesis in hASCs encapsulated in collagen‐based hydrogels was tested with heterotopic bone formation assay in nude mice. Our research found that circFOXP1 was significantly down‐regulated in OP patient bone tissues and functioned like a miRNA sponge targeting miR‐33a‐5p to increase FOXP1 expression. In vivo and in vitro analyses showed that circFOXP1 enhances hASC osteogenesis by sponging miR‐33a‐5p. Conversely, miR‐33a‐5p inhibits osteogenesis by targeting FOXP1 3′‐UTR and down‐regulating FOXP1 expression. These results determined that circFOXP1 binding to miR‐33a‐5p promotes hASC osteogenic differentiation by targeting FOXP1. Therefore, circFOXP7ay prevent OP and can be used as a candidate OP therapeutic target.