Molecular Imaging of Collagen Destruction of the Spine

Lei Liu, Kui Huang, Wei Li, Rongmao Qiu, Yijie Fang, Yongjie Huang, Suwen Zhao, Hai Lv, Kuibo Zhang, Hong Shan, Yang Li

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)19138-19149
Number of pages12
JournalACS Nano
Volume15
Issue number12
DOIs
StatePublished - Dec 28 2021

Keywords

  • collagen triple helix
  • facet joint
  • intervertebral disc degeneration
  • microdestruction
  • spinal disorder

ASJC Scopus subject areas

  • General Engineering
  • General Materials Science
  • General Physics and Astronomy

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