Fibroblast growth factor 23 regulates hypoxia‑induced osteoblast apoptosis through the autophagy‑signaling pathway
- Qipu Yin
- Hongxia Yang
- Lun Fang
- Qi Wu
- Shan Gao
- Yadi Wu
- Lu Zhou
- Published online on: September 8, 2023 https://doi.org/10.3892/mmr.2023.13086
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Hypoxia can lead to programmed osteoblast death. Prevention of osteoblast apoptosis caused by hypoxia is of great significance in the study of the occurrence and development of bone necrosis. The present study aimed to investigate the effects and mechanism of fibroblast growth factor 23 (FGF23) on hypoxia‑induced apoptosis in primary osteoblasts and MC3T3‑E1 cells osteoblasts. Cells were transfected with a plasmid carrying the FGF23 gene and a cell model of hypoxia‑induced apoptosis was established. FGF23 mRNA levels were measured using reverse transcription‑quantitative (RT‑q) PCR and western blotting was used to assess protein levels. Apoptosis was analyzed by MTT assay, fluorescein diacetate and ethidium bromide staining, flow cytometry and RT‑qPCR and western blotting were used to verify the mRNA and protein levels of apoptosis‑ and autophagy‑related gene mRNA. The targeted relationship between miR‑17‑5p and FGF23 was confirmed using the StarBase database, TargetScan database and a luciferase reporter assay. FGF23 decreased cell survival and increased the rate of apoptosis. The mRNA and protein expression of the pro‑apoptotic genes Bax and caspases 3 and 9 increased, whereas that of the anti‑apoptotic Bcl‑2 decreased. The expressions of the autophagy‑associated proteins beclin‑1, light chain 3‑II (LC3‑II) and the LC3‑II/LC3‑I ratio were significantly increased. In addition, a luciferase reporter assay confirmed that FGF23 directly regulated micro RNA (miR)‑17‑5p. The effects of FGF23 silencing were reversed by miR‑17‑5p inhibition. FGF23 may regulate hypoxia‑induced osteoblast apoptosis by targeting miR‑17‑5p through the autophagy‑signaling pathway. This provides a rationale for FGF23 as a potential therapeutic target for osteonecrosis of the femoral head.