{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T13:48:56Z","timestamp":1778680136318,"version":"3.51.4"},"reference-count":34,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2022,5,14]],"date-time":"2022-05-14T00:00:00Z","timestamp":1652486400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cell Proliferation"],"published-print":{"date-parts":[[2022,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objectives<\/jats:title><jats:p>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\u20101 for ethanol\u2010induced ONFH.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and Methods<\/jats:title><jats:p>The ethanol\u2010induced ONFH in rat was performed to explore the protective of Alda\u20101 by various experimental methods. Subsequently, the effect of Alda\u20101 and ethanol on the osteogenic and adipogenic differentiation was investigated via multiple cellular and molecular methods. Finally, the effect of Alda\u20101 and ethanol on the neo\u2010vascularization was detected in Human umbilical vein endothelial cells (HUVECs) and ONFH model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Firstly, radiographical and pathological measurements indicated that alda\u20101 protected ethanol\u2010induced ONFH. Moreover, ethanol significantly inhibited the proliferation and osteogenic differentiation of BMSCs, whereas Alda\u20101 could distinctly rescue it by PI3K\/AKT signalling. Secondly, ethanol remarkably promoted the lipid vacuoles formation of BMSCs, while Alda\u20101 significantly retarded it on BMSCs by AMPK signalling pathway. Finally, ethanol significantly inhibited proliferation and growth factor level resulting in reduced angiogenesis, whereas Alda\u20101 could rescue the effect of ethanol. Additionally, Alda\u20101 significantly reduced the occurrence of ONFH and promoted vessel number and distribution in alcoholic ONFH.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Alda\u20101 activation of ALDH 2 was highly demonstrated to protect ethanol\u2010induced ONFH by triggering new bone formation, reducing adipogenesis and stimulating vascularization.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cpr.13252","type":"journal-article","created":{"date-parts":[[2022,5,14]],"date-time":"2022-05-14T10:58:58Z","timestamp":1652525938000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Activation of aldehyde dehydrogenase 2 protects ethanol\u2010induced osteonecrosis of the femoral head in rat model"],"prefix":"10.1111","volume":"55","author":[{"given":"Xiaoyi","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Orthopedic Surgery The First Affiliated Hospital of Xiamen University  Xiamen People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daoming","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Medical Imaging The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture  Enshi People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaiyang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Spine Surgery Drum Tower Hospital of Nanjing University Medical School  Nanjing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pengbo","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Shanghai Jiao Tong University Affiliated Sixth People's Hospital  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gang","family":"Rui","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery The First Affiliated Hospital 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