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Selective Enzymatic Digestion of Proteoglycans and Collagens Alters Cartilage T1rho and T2 Relaxation Times

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Abstract

Our objective was to determine the relationship of T1rho and T2 relaxation mapping to the biochemical and biomechanical properties of articular cartilage through selective digestion of proteoglycans and collagens. Femoral condyles were harvested from porcine knee joints and treated with either chondroitinase ABC (cABC) followed by collagenase, or collagenase followed by cABC. Magnetic resonance images were acquired and cartilage explants were harvested for biochemical, biomechanical, and histological analyses before and after each digestion. Targeted enzymatic digestion of proteoglycans with cABC resulted in elevated T1rho relaxation times and decreased sulfated glycosaminoglycan content without affecting T2 relaxation times. In contrast, extractable collagen and T2 relaxation times were increased by collagenase digestion; however, neither was altered by cABC digestion. Aggregate modulus decreased with digestion of both components. Overall, we found that targeted digestion of proteoglycans and collagens had varying effects on biochemical, biomechanical, and imaging properties. T2 relaxation times were altered with changes in extractable collagen, but not changes in proteoglycan. However, T1rho relaxation times were altered with proteoglycan loss, which may also coincide with collagen disruption. Since it is unclear which matrix components are disrupted first in osteoarthritis, both markers may be important for tracking disease progression.

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Acknowledgments

The authors would like to thank the National Institutes of Health (AR065527, AR066477, AG15768, AG028716, AG46927), the Veteran’s Affairs Rehabilitation Research Service Award, the Orthopaedic Research and Education Foundation, and the AO Foundation for financial support of this work. Additionally, the authors would like to thank the Duke Center for Advanced Magnetic Resonance Development (CAMRD) for their assistance with MR imaging.

Conflict of interest

The authors have no conflicts of interest.

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Authors and Affiliations

  1. Department of Orthopaedic Surgery, Duke University School of Medicine, Durham, NC, USA

    Amber T. Collins, Courtney C. Hatcher, Sophia Y. Kim, Sophia N. Ziemian, Louis E. DeFrate & Amy L. McNulty

  2. Department of Radiology, Duke University School of Medicine, Durham, NC, USA

    Charles E. Spritzer

  3. Department of Pathology, Duke University School of Medicine, Durham, NC, USA

    Amy L. McNulty

  4. Department of Biomedical Engineering, Duke University, Durham, NC, USA

    Sophia Y. Kim & Louis E. DeFrate

  5. Department of Mechanical Engineering and Materials Science, Duke University, Durham, NC, USA

    Louis E. DeFrate

  6. Department of Orthopaedic Surgery, Washington University and Shriners Hospital for Children, St. Louis, MO, USA

    Farshid Guilak

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Collins, A.T., Hatcher, C.C., Kim, S.Y. et al. Selective Enzymatic Digestion of Proteoglycans and Collagens Alters Cartilage T1rho and T2 Relaxation Times. Ann Biomed Eng 47, 190–201 (2019). https://doi.org/10.1007/s10439-018-02143-7

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