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Molecular Imaging of Collagen Destruction of the Spine

  • Lei Liu
    Lei Liu
    Guangdong Provincial Key Laboratory of Biomedical Imaging and Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai 519000, China
    Department of Spine Surgery, the Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai 519000, China
    More by Lei Liu
  • Kui Huang
    Kui Huang
    Guangdong Provincial Key Laboratory of Biomedical Imaging and Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai 519000, China
    More by Kui Huang
  • Wei Li
    Wei Li
    Department of Pathology, the Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai 519000, China
    More by Wei Li
  • Rongmao Qiu
    Rongmao Qiu
    Guangdong Provincial Key Laboratory of Biomedical Imaging and Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai 519000, China
    More by Rongmao Qiu
  • Yijie Fang
    Yijie Fang
    Department of Radiology, the Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai 519000, China
    More by Yijie Fang
  • Yongjie Huang
    Yongjie Huang
    Guangdong Provincial Key Laboratory of Biomedical Imaging and Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai 519000, China
  • Suwen Zhao
    Suwen Zhao
    Guangdong Provincial Key Laboratory of Biomedical Imaging and Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai 519000, China
    More by Suwen Zhao
  • Hai Lv
    Hai Lv
    Department of Spine Surgery, the Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai 519000, China
    More by Hai Lv
  • Kuibo Zhang*
    Kuibo Zhang
    Department of Spine Surgery, the Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai 519000, China
    *Email: [email protected]
    More by Kuibo Zhang
  • Hong Shan*
    Hong Shan
    Guangdong Provincial Key Laboratory of Biomedical Imaging and Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai 519000, China
    Department of Interventional Medicine, the Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai 519000, China
    *Email: [email protected]
    More by Hong Shan
  • , and 
  • Yang Li*
    Yang Li
    Guangdong Provincial Key Laboratory of Biomedical Imaging and Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai 519000, China
    *Email: [email protected]
    More by Yang Li
Cite this: ACS Nano 2021, 15, 12, 19138–19149
Publication Date (Web):November 5, 2021
https://doi.org/10.1021/acsnano.1c07112
Copyright © 2021 American Chemical Society

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    Supporting Info (7)»

    Abstract

    Abstract Image

    As the leading cause of disability worldwide, low back pain is commonly caused by biomechanical and catabolic disruptions to key structures of the spine, such as intervertebral discs and facet joints. To date, accurate, noninvasive detection of microdestruction within these tissues remains an elusive goal. Here, we report an in vivo imaging approach based on a collagen hybridizing peptide (CHP) that specifically targets disruption to the extracellular matrix architecture at the molecular scale─the denatured collagen molecules. Utilizing fluorescently labeled CHPs, live animal imaging, and light sheet fluorescence microscopy, we mapped collagen destruction in the lumbar spines in 3D, revealing that under normal conditions collagen destruction was localized to load-bearing anatomical structures including annulus fibrosus of the disc and the facet joints, where aging, tensile force (hindlimb suspension), and disc degeneration (needle puncture) escalated the CHP-binding in specific mouse models. We showed that targeting denatured collagen molecules allowed for an accurate, quantifiable interrogation of the structural integrity of these spinal matrixes with a greater sensitivity than anatomical imaging and histology. Finally, we demonstrated CHP’s binding to degenerated human discs, suggesting exciting potentials for applying CHP for diagnosing, monitoring, and treating various spinal disorders, including intervertebral disc degeneration, facet joint osteoarthritis, and ankylosing spondylitis.

    Supporting Information

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    The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acsnano.1c07112.

    • Methods of MRI and micro-computed tomography and histology, tables of fluorescently-labeled peptides used in this study and their MALDI MS information and in vivo near-infrared fluorescence probes and the imaging parameters used, and figures of representative NIRF images, fluorescence micrographs, HPLC traces, and CHP fluorescence signal (PDF)

    • Movie S1: 3D scan showing Cy5-CHP’s in vivo binding to damaged collagen molecules within a clear segment of lumbar spine, harvested from an SD rat (MP4)

    • Movie S2a: 3D scan showing Cy5-CHP’s in vivo binding to damaged collagen molecules within cleared lumbar spine specimens harvested from a 24-month old mouse (MP4)

    • Movie S2b: 3D scan showing Cy5-CHP’s in vivo binding to damaged collagen molecules within cleared lumbar spine specimens harvested from a 2-month old mouse (MP4)

    • Movie S3a: 3D scan showing Cy5-CHP’s in vivo binding to damaged collagen molecules within cleared lumbar spine specimens collected from a hindlimb suspended mouse (MP4)

    • Movie S3b: 3D scan showing Cy5-CHP’s in vivo binding to damaged collagen molecules within cleared lumbar spine specimens collected from a normal control mouse (MP4)

    • Movie S4: 3D scan showing Cy5-CHP’s in vivo binding to damaged collagen molecules within a cleared lumbar spine specimen collected from a C57BL/6 mouse, whose L4/L5 disc has been needle-punctured (MP4)

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    Most electronic Supporting Information files are available without a subscription to ACS Web Editions. Such files may be downloaded by article for research use (if there is a public use license linked to the relevant article, that license may permit other uses). Permission may be obtained from ACS for other uses through requests via the RightsLink permission system: http://pubs.acs.org/page/copyright/permissions.html.

    Cited By

    This article is cited by 5 publications.

    1. Xiaojing Li, Qi Zhang, S. Michael Yu, Yang Li. The Chemistry and Biology of Collagen Hybridization. Journal of the American Chemical Society 2023, 145 (20) , 10901-10916. https://doi.org/10.1021/jacs.3c00713
    2. Qi Zhang, Xiaojing Li, Kui Huang, Yongjie Huang, Suwen Zhao, Shanshan Liu, Yang Li. Controlling the Trimerization of the Collagen Triple-Helix by Solvent Switching. Biomacromolecules 2023, 24 (4) , 1689-1699. https://doi.org/10.1021/acs.biomac.2c01475
    3. Noah Fine, Starlee Lively, Cheryle Ann Séguin, Anthony V. Perruccio, Mohit Kapoor, Raja Rampersaud. Intervertebral disc degeneration and osteoarthritis: a common molecular disease spectrum. Nature Reviews Rheumatology 2023, 19 (3) , 136-152. https://doi.org/10.1038/s41584-022-00888-z
    4. Di Wu, Gaocai Li, Xingyu Zhou, Weifeng Zhang, Huaizhen Liang, Rongjin Luo, Kun Wang, Xiaobo Feng, Yu Song, Cao Yang. Repair Strategies and Bioactive Functional Materials for Intervertebral Disc. Advanced Functional Materials 2022, 32 (52) , 2209471. https://doi.org/10.1002/adfm.202209471
    5. Yi Zheng, Liangwei Mei, Shengyou Li, Teng Ma, Bing Xia, Yiming Hao, Xue Gao, Bin Wei, Yitao Wei, Da Jing, Zhuojing Luo, Jinghui Huang. Pulsed Electromagnetic Field Alleviates Intervertebral Disc Degeneration by Activating Sirt1-Autophagy Signaling Network. Frontiers in Bioengineering and Biotechnology 2022, 10 https://doi.org/10.3389/fbioe.2022.853872

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