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Adiponectin overexpression promotes fracture healing through regulating the osteogenesis and adipogenesis balance in osteoporotic mice

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Journal of Bone and Mineral Metabolism Aims and scope Submit manuscript

Abstract

Introduction

Osteoporosis invariably manifests as loss of bone, which is replaced by adipose tissue; this can easily lead to fractures, accompanied by delayed and poor healing. Adiponectin (APN) balances osteogenesis and adipogenesis in bone marrow mesenchymal stem cells (BMSCs). Therefore, this study explored whether adiponectin promotes bone fracture healing by regulating the balance between osteogenesis and adipogenesis.

Materials and methods

We used adenovirus overexpression vectors carrying APN (Ad-APN-GFP) to treat ovariectomized (OVX) mouse BMSCs and osteoporotic bone fractures to investigate the role of APN in bone microenvironment metabolism in osteoporotic fractures. We subsequently established an OVX mice and bone fracture model using Ad-APN-GFP treatment to investigate whether APN could promote bone fracture healing in osteoporotic mice.

Results

The experimental results showed that APN is a critical molecule in diverse differentiation directions in OVX mouse BMSCs, with pro-osteogenesis and anti-adipogenesis properties. Importantly, our study revealed that Ad-APN-GFP treatment facilitates bone generation and healing around the osteoporotic fracture ends. Moreover, we identified that Sirt1 and Wnt signaling were closely related to the pro-osteogenesis and anti-adipogenesis commitment of APN in OVX mouse BMSCs and femoral tissues.

Conclusion

We demonstrated that APN overexpression facilitates bone fracture healing in osteoporosis. Furthermore, APN overexpression promoted bone formation in OVX mouse BMSCs and bone fracture ends by regulating the balance between osteogenesis and adipogenesis both in vitro and in vivo.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (81970917 and 82001018) and the Research and Develop Program, West China Hospital of Stomatology Sichuan University (RD-03-202102). The authors would like to thank the State Key Laboratory of Oral Disease & National Clinical Research Center for Oral Diseases of Sichuan University West China Hospital of Stomatology for their assistance with μCT analysis, animal surgeries experiments, staining slices, and other experiments.

Funding

Funding was provided by Research and Develop Program, West China Hospital of Stomatology Sichuan University (Grant no. RD-03-202102) and National Natural Science Foundation of China (Grant nos. 81970917, 82001018).

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Authors and Affiliations

  1. State Key Laboratory of Oral Disease and National Clinical Research Center for Oral Diseases and Department of Oral Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China

    Ju Zhang, Shibo Liu, Ze He, Hanghang Liu, Yao Liu, Pei Hu & En Luo

  2. College of Polymer Science and Engineering, State Key Laboratory of Polymer Materials Engineering, Sichuan University, Chengdu, 610065, China

    Zhongming Li & Jiazhuang Xu

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  1. Ju Zhang
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  9. En Luo
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Contributions

EL: methodology, validation, investigation, and writing—review and editing and funding acquisition. JZ: conceptualization, methodology, validation, formal analysis, investigation, writing—original draft and review and editing, visualization, supervision, and project administration. SL, ZH: methodology, resources, supervision, and writing—review and editing. HL, YL, PH, ZL, JX: methodology, validation, investigation, and writing—review and editing.

Corresponding author

Correspondence to En Luo.

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The authors declared that there are no competing interests.

Ethical approval

The Ethics Review Committee for Animal Experimentation of West China Hospital of Stomatology Sichuan University approved the experimental protocol of this study. All animal experiments were conducted in accordance with the Institutional principles for the concern and use of animals. This study does not involve human body and clinical study.

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Zhang, J., Liu, S., He, Z. et al. Adiponectin overexpression promotes fracture healing through regulating the osteogenesis and adipogenesis balance in osteoporotic mice. J Bone Miner Metab 41, 457–469 (2023). https://doi.org/10.1007/s00774-023-01420-3

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  • DOI: https://doi.org/10.1007/s00774-023-01420-3

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