Department of Orthopedic Surgery, The First Affiliated Hospital of Xiamen University, Xiamen, People's Republic of China.
Department of Medical Imaging, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, People's Republic of China.
Cell Prolif. 2022 Jun;55(6):e13252. doi: 10.1111/cpr.13252. Epub 2022 May 14.
Osteonecrosis of the femoral head (ONFH) is a devastating disease characterized by destructive bone structures, enlarged adipocyte accumulation and impaired vascularization. The aldehyde dehydrogenase 2 (ALDH 2) is the limiting enzyme for ethanol metabolism with many physiological functions. The aim was investigated the potential protective role of activated ALDH 2 by Alda-1 for ethanol-induced ONFH.
The ethanol-induced ONFH in rat was performed to explore the protective of Alda-1 by various experimental methods. Subsequently, the effect of Alda-1 and ethanol on the osteogenic and adipogenic differentiation was investigated via multiple cellular and molecular methods. Finally, the effect of Alda-1 and ethanol on the neo-vascularization was detected in Human umbilical vein endothelial cells (HUVECs) and ONFH model.
Firstly, radiographical and pathological measurements indicated that alda-1 protected ethanol-induced ONFH. Moreover, ethanol significantly inhibited the proliferation and osteogenic differentiation of BMSCs, whereas Alda-1 could distinctly rescue it by PI3K/AKT signalling. Secondly, ethanol remarkably promoted the lipid vacuoles formation of BMSCs, while Alda-1 significantly retarded it on BMSCs by AMPK signalling pathway. Finally, ethanol significantly inhibited proliferation and growth factor level resulting in reduced angiogenesis, whereas Alda-1 could rescue the effect of ethanol. Additionally, Alda-1 significantly reduced the occurrence of ONFH and promoted vessel number and distribution in alcoholic ONFH.
Alda-1 activation of ALDH 2 was highly demonstrated to protect ethanol-induced ONFH by triggering new bone formation, reducing adipogenesis and stimulating vascularization.
股骨头坏死（ONFH）是一种破坏性疾病，其特征为骨结构破坏、脂肪细胞堆积增大以及血管生成受损。醛脱氢酶 2（ALDH 2）是乙醇代谢的限速酶，具有多种生理功能。本研究旨在探讨激活型 ALDH 2 对乙醇诱导的 ONFH 的潜在保护作用。
通过各种实验方法研究乙醇诱导的大鼠 ONFH，以探讨 Alda-1 的保护作用。随后，通过多种细胞和分子方法研究 Alda-1 和乙醇对成骨和成脂分化的影响。最后，在人脐静脉内皮细胞（HUVEC）和 ONFH 模型中检测 Alda-1 和乙醇对新生血管形成的影响。
首先，影像学和病理学测量表明 Alda-1 可保护乙醇诱导的 ONFH。此外，乙醇显著抑制 BMSCs 的增殖和成骨分化，而 Alda-1 通过 PI3K/AKT 信号通路可显著挽救这一作用。其次，乙醇显著促进 BMSCs 中脂质空泡的形成，而 Alda-1 通过 AMPK 信号通路显著抑制这一作用。最后，乙醇显著抑制增殖和生长因子水平，导致血管生成减少，而 Alda-1 可挽救乙醇的作用。此外，Alda-1 可显著减少酒精性 ONFH 的发生，并促进血管数量和分布。
ALDH 2 激活 Alda-1 可通过触发新骨形成、减少脂肪生成和刺激血管生成，高度显示对乙醇诱导的 ONFH 具有保护作用。
