Zoledronic acid relieves steroid-induced avascular necrosis of femoral head via inhibiting FOXD3 mediated ANXA2 transcriptional activation.

Autor: Lin Y; Department of Orthopedics, Fujian Medical University Union Hospital, Fuzhou 350000, Fujian Province, PR China; Department of Orthopedics, Fujian Pingtan Comprehensive Experimental Area Hospital, Fuzhou 350400, Fujian Province, PR China., Chen M; Department of Orthopedics, Fujian Medical University Union Hospital, Fuzhou 350000, Fujian Province, PR China., Guo W; Department of Pathology, Pingtan Comprehensive Experimental Area Hospital, Fuzhou 350400, Fujian Province, PR China., Qiu S; Department of Pathology, Fujian Medical University Union Hospital, Fuzhou 350000, Fujian Province, PR China., Chen L; Laboratory Medicine, Fujian Pingtan Comprehensive Experimental Area Hospital, Fuzhou 350400, Fujian Province, PR China. Electronic address: leifchenfly@163.com., Liu W; Department of Orthopedics, Fujian Medical University Union Hospital, Fuzhou 350000, Fujian Province, PR China. Electronic address: wengeunion@fjmu.edu.cn.
Jazyk: angličtina
Zdroj: Bone [Bone] 2024 Nov; Vol. 188, pp. 117222. Date of Electronic Publication: 2024 Aug 03.
DOI: 10.1016/j.bone.2024.117222
Abstrakt: Background: Zoledronic acid (ZOL) is a type of bisphosphonate with good therapeutic effects on orthopaedic diseases. However, the pharmacological functions of ZOL on steroid-induced avascular necrosis of femoral head (SANFH) and the underlying mechanism remain unclear, which deserve further research.
Methods: SANFH models both in vivo and in vitro were established by dexamethasone (Dex) stimulation. Osteoclastogenesis was examined by TRAP staining. Immunofluorescence was employed to examine autophagy marker (LC3) level. Cell apoptosis was analyzed by TUNEL staining. The interaction between Foxhead box D3 protein (FOXD3) and Annexin A2 (ANXA2) promoter was analyzed using ChIP and dual luciferase reporter gene assays.
Results: Dex aggravated osteoclastogenesis and induced osteoclast differentiation and autophagy in vitro, which was abrogated by ZOL treatment. PI3K inhibitor LY294002 abolished the inhibitory effect of ZOL on Dex-induced osteoclast differentiation and autophagy. FOXD3 overexpression neutralized the downregulation effects of ZOL on Dex-induced osteoclasts by transcriptionally activating ANXA2. ANXA2 knockdown reversed the effect of FOXD3 overexpression on ZOL-mediated biological effects in Dex-treated osteoclasts. In addition, ZOL improved SANFH symptoms in rats.
Conclusion: ZOL alleviated SANFH through regulating FOXD3 mediated ANXA2 transcriptional activity and then promoting PI3K/AKT/mTOR pathway, revealing that FOXD3 might be a target for ZOL in SANFH treatment.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024. Published by Elsevier Inc.)
Databáze: MEDLINE
Externí odkaz: