Department of Orthopaedics, Affiliated Hospital 2 of Nantong University, Nantong University, Nantong, 226000, Jiangsu, People's Republic of China.
Department of Orthopaedics, Huangshi Central Hospital (Affiliated Hospital of Hubei Polytechnic University), Edong Healthcare Group, Huangshi, 435000, Hubei, People's Republic of China.
J Orthop Surg Res. 2021 Apr 20;16(1):272. doi: 10.1186/s13018-021-02386-6.
The purpose of the current study was to explore the role and underlying mechanism of cellular retinoic acid binding protein 2 (CRABP2) in dexamethasone (DEX)-induced apoptosis in human osteoblast cells.
GSE10311 was downloaded from the Gene Expression Omnibus (GEO) database to identify the differentially expressed genes (DEGs) by the limma/R package. Primary human osteoblast was isolated and treated with different concentration of DEX (0, 10, 10, 10, 10, and 10 mol/L), and cell viability and flow cytometry were used to detect cell proliferation and apoptosis. A CRABP2 overexpression plasmid (oe-CRABP2) was used to overexpress CRABP2, and western blotting was conducted to detect protein expression.
We found that CRABP2 was downregulated in the DEX-treated group. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses indicated that DEGs were associated with PI3K/Akt signaling pathway. DEX downregulated CRABP2 gene and protein expression, inhibited viability, and induced human osteoblast apoptosis. Overexpression of CRABP2 reversed DEX-induced apoptosis in human osteoblast. Moreover, overexpression of CRABP2 delayed the progression of DEX-induced osteonecrosis of the femoral head (ONFH) animal model.
In conclusion, CRABP2 is effective at inhibiting DEX-induced human osteoblast apoptosis and delayed ONFH progression.
本研究旨在探讨细胞视黄醇结合蛋白 2（CRABP2）在地塞米松（DEX）诱导人成骨细胞凋亡中的作用及潜在机制。
从基因表达综合数据库（GEO）下载 GSE10311 数据集，利用 limma/R 包分析差异表达基因（DEGs）。分离原代人成骨细胞，用不同浓度的 DEX（0、10、10、10、10 和 10 mol/L）处理细胞，采用细胞活力和流式细胞术检测细胞增殖和凋亡。用 CRABP2 过表达质粒（oe-CRABP2）过表达 CRABP2，用 Western blot 检测蛋白表达。
我们发现 DEX 处理组中 CRABP2 下调。京都基因与基因组百科全书（KEGG）通路分析表明，DEGs 与 PI3K/Akt 信号通路有关。DEX 下调 CRABP2 基因和蛋白表达，抑制细胞活力，并诱导人成骨细胞凋亡。CRABP2 的过表达逆转了 DEX 诱导的人成骨细胞凋亡。此外，CRABP2 的过表达延缓了 DEX 诱导的股骨头坏死（ONFH）动物模型的进展。
总之，CRABP2 能有效抑制 DEX 诱导的人成骨细胞凋亡，延缓 ONFH 进展。
