lncRNA FGD5-AS1 Regulates Bone Marrow Stem Cell Proliferation and Apoptosis by Affecting miR-296-5p/STAT3 Axis in Steroid-Induced Osteonecrosis of the Femoral Head

Abstract

Background. Osteonecrosis of the femoral head (ONFH) is a common hip joint disease, which is more harmful and seriously affects the lives of patients. This study aims to clarify the regulatory mechanism of lncRNA FGD5-AS1 in ONFH. Methods. The expression of the protein and mRNA was detected by RT-qPCR and Western blot assay. The regulatory mechanism of lncRNA FGD5-AS1 was detected by the dual-luciferase reporter assay, CCK-8 assay, and flow cytometry assay. Results. Dex can inhibit cell proliferation and differentiation and induce apoptosis in hBMSCs in a dose-dependent manner. Overexpression of lncRNA FGD5-AS1 promoted cell proliferation and restrained apoptosis in Dex-treated hBMSCs. In addition, lncRNA FGD5-AS1 acts as a sponge for miR-296-5p. Also, miR-296-5p directly targets STAT3. More importantly, miR-296-5p and STAT3 can affect the function of lncRNA FGD5-AS1 in Dex-treated hBMSCs. Conclusion. lncRNA FGD5-AS1 promotes cell proliferation and inhibits apoptosis in steroid-induced ONFH through acting as a sponge for miR-296-5p and upregulation of STAT3.

Comprehensive analysis of circRNA expression profiles in postmenopausal women differing in bone mineral density

“…[35,36] Moreover, hsa-miR-296-5p directly targeted signal transducer and activator of transcription 3 (STAT3), inhibiting its mRNA and protein expression and reducing the proliferation and differentiation of bone marrow stem cells. [37] Unfortunately, hsa-miR-635 has been rarely studied, which explained why we failed to find its direct role played in the skeletal system. In one study, however, circRANBP17 was reported to up-regulate the expression level of runt-related transcription factor 2 (RUNX2) by sponging hsa-miR-635, promoting the proliferation and invasion of nasopharyngeal carcinoma.…”

“…[35,36] Moreover, hsa-miR-296-5p directly targeted signal transducer and activator of transcription 3 (STAT3), inhibiting its mRNA and protein expression and reducing the proliferation and differentiation of bone marrow stem cells. [37]…”

Insight into Steroid-Induced ONFH: The Molecular Mechanism and Function of Epigenetic Modification in Mesenchymal Stem Cells

“…The ceRNA mechanism also plays a key role in the classical axis OPG/RANK/RANKL that regulates osteoblast-osteoclast bone homeostasis. LncNORAD and lncFGD5-AS1, as ceR-NAs, target miR-26a-5p and miR-296-5p/STAT3, respectively, to regulate the major signaling pathways of osteoclast differentiation and bone resorption [18,65]. LncRNA/circRNA, as a ceRNA, is also involved in regulating other proliferation-and apoptosis-related pathways, including PI3K/Akt, Bad/Bcl-2, TGF-β, etc.…”