Activation of osteoblast ferroptosis by risperidone accelerates bone loss in mice models of schizophrenia.

IF 2.8 3区医学 Q1 ORTHOPEDICS

Journal of Orthopaedic Surgery and Research Pub Date : 2025-01-23 DOI:10.1186/s13018-025-05520-w

Hongyan Fan, Zaihong Yang, Lan Pang, Peifan Li, Changrong Duan, Guangyuan Xia, Lei Zheng

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引用次数: 0

Abstract

Background: Ferroptosis is an iron-dependent regulatory cell death, which plays an essential role in bone loss. This study investigated whether the mechanism of risperidone (RIS)-induced bone loss is related to ferroptosis.

Methods: The schizophrenia mice were induced by administering MK-801. Subsequently, RIS were injected, or ferroptosis inhibitor Ferrostatin-1 (Fer-1) co-injected for 8 weeks. Bone loss of schizophrenia mice were assessed using microCT, H&E staining, ALP staining, ARS staining and WB, respectively. Ferroptosis of schizophrenia mice were detected by Iron Colorimetric Assay Kit and WB, respectively. In addition, ALP staining, ARS staining, and WB were performed to reveal the role of RIS in osteogenic differentiation of MC3T3-E1 and BMSCs cells.

Results: RIS treatment facilitates bone loss in schizophrenia mice and inhibit osteogenic differentiation of MC3T3-E1 and BMSCs cells. Moreover, up-regulated ferroptosis was found in vivo and in vitro after RIS treatment. Interesting, the bone loss and inhibition of osteogenic differentiation induced by RIS in schizophrenia mice were reversed by ferroptosis inhibitor Fer-1.

Conclusion: Ferroptosis induced by RIS aggravates the bone loss of schizophrenia mice via inhibiting osteogenic differentiation.

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来源期刊

Journal of Orthopaedic Surgery and Research ORTHOPEDICS-

CiteScore

4.10

自引率

7.70%

发文量

494

审稿时长

>12 weeks

期刊介绍： Journal of Orthopaedic Surgery and Research is an open access journal that encompasses all aspects of clinical and basic research studies related to musculoskeletal issues. Orthopaedic research is conducted at clinical and basic science levels. With the advancement of new technologies and the increasing expectation and demand from doctors and patients, we are witnessing an enormous growth in clinical orthopaedic research, particularly in the fields of traumatology, spinal surgery, joint replacement, sports medicine, musculoskeletal tumour management, hand microsurgery, foot and ankle surgery, paediatric orthopaedic, and orthopaedic rehabilitation. The involvement of basic science ranges from molecular, cellular, structural and functional perspectives to tissue engineering, gait analysis, automation and robotic surgery. Implant and biomaterial designs are new disciplines that complement clinical applications. JOSR encourages the publication of multidisciplinary research with collaboration amongst clinicians and scientists from different disciplines, which will be the trend in the coming decades.