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Interleukin-19 in Bone Marrow Contributes to Bone Loss Via Suppressing Osteogenic Differentiation Potential of BMSCs in Old Mice

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Abstract

Background

Cellular senescence is an important process related to the pathogenic mechanism of different disorders, especially bone loss. During senescence, bone marrow stromal cells (BMSCs) lose their self-renewal and functional differentiation abilities. Therefore, finding signals opposing the osteogenic differentiation of BMSCs within bone marrow microenvironment is the important for elucidating these above-mentioned mechanisms. Inflammatory cytokines affect bone physiology and remodeling. However, the function of interleukin-19 (IL-19) in skeletal system remains unclear.

Methods

The mouse model of IL-19 knockout was established through embryonic stem cell injection for analyzing how IL-19 affected bone formation. Micro-CT examinations were performed to evaluate bone microstructures. We performed a three-point bending test to measure bone stiffness and the ultimate force. Antibody arrays were performed to detect interleukin family members in bone marrow aspirates. BMSCs were cultured and induced for osteogenic differentiation.

Results

According to our findings, there was increased IL-19 accumulation within bone marrow in old mice relative to that in their young counterparts, resulting in bone loss via the inhibition of BMSCs osteogenic differentiation. Among Wnt/β-catenin pathway members, IL-19 strongly upregulated sFRP1 via STAT3 phosphorylation. The inhibition of STAT3 and sFRP1 abolished IL-19’s inhibition against the BMSCs osteogenic differentiation.

Conclusion

To sum up, IL-19 inhibited BMSCs osteogenic differentiation in old mice. Our findings shed novel lights on pathogenic mechanism underlying age-related bone loss and laid a foundation for further research on identifying novel targets to treat senile osteoporosis.

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Data Availability

All data generated or analyzed during this study are included in this published article.

Code Availability

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Funding

This research was principally supported by the Shanghai Natural Science Foundation (Grant No. 19ZR1440700). Additional funding was provided by the Shanghai Pujiang Program, under the auspices of the Science and Technology Commission of Shanghai Municipality (Grant No. 16PJ0004679), and the Medical-Industrial Interdisciplinary Research Fund of Shanghai Jiaotong University (Grant No. YG2017MS02). The project also received support from the Youth Science and Technology Innovation Studio of Shanghai Jiao Tong University School of Medicine (Grant No. JYKCGZS8) and the Practice Training Base for Interdisciplinary Innovative Talents of Shanghai Jiao Tong University (Grant No. SJTUJXCX-3).

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Author notes

  1. Enjun He, Haitao Sui and Hongjie Wang contributed equally to this work.

Authors and Affiliations

  1. Department of Orthopedics, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

    Enjun He, Hongjie Wang, Weihong Guo, Zhicheng Dai & Qinghua Zhao

  2. Department of Orthopaedics, Dongying People’s Hospital, Dongying, Shandong, China

    Haitao Sui

  3. Department of Surgery of Spine and Spinal Cord, People’s Hospital of Henan University, Henan Provincial People’s Hospital, Henan, Zhengzhou, China

    Xiang Zhao

  4. Department of Pediatric Orthopaedics, Shanghai Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

    Zhenkai Wu

  5. Department of Orthopedics, Zhabei Central Hospital of Jing’an District, Shanghai, China

    Kai Huang

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  1. Enjun He
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Contributions

QZ supervised the study. Research design was a collaborative effort by QZ, KH, and ZW. EH and HS conducted most experiments, while EH and HW analyzed the data. The manuscript was written by EH, HS, and HW. XZ, WG, and ZD contributed to the discussion section with insightful suggestions.QZ provided overall guidance. All authors discussed the results and commented on the paper.

Corresponding authors

Correspondence to Kai Huang or Qinghua Zhao.

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Ethics Approval and Consent to Participate

All mice were maintained under SPF conditions in the animal facility of in the Animal Laboratory Unit of Shanghai General Hospital, Shanghai Jiaotong University School of Medicine (Shanghai, China). All experiments were performed with the protocol approved by the Animal Care and Use Committee of Shanghai General Hospital, Shanghai Jiaotong University School of Medicine(Title of the approved project: Interleukin-19 in bone marrow contributes to bone loss via suppressing osteogenic differentiation potential of BMSCs in old mice; Approval number: 2020AWS0023; Date of approval: March 26, 2020).

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He, E., Sui, H., Wang, H. et al. Interleukin-19 in Bone Marrow Contributes to Bone Loss Via Suppressing Osteogenic Differentiation Potential of BMSCs in Old Mice. Stem Cell Rev and Rep (2024). https://doi.org/10.1007/s12015-024-10709-3

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