Original Research ArticlesThe Inner Annulus Fibrosus Encroaches on the Nucleus Pulposus in the Injured Mouse Tail Intervertebral DiscWei, Yulong MD, PhD; Tian, Zuozhen MS; Tower, Robert J. PhD; E. Gullbrand, Sarah PhD; Yao, Lutian MD; Shetye, Snehal S. PhD; Mauck, Robert L. PhD; Qin, Ling PhD; Zhang, Yejia MD, PhD Author Information From the Departments of Orthopaedic Surgery (YW, RJT, SEG, LY, SSS, RLM, LQ, YZ) and Physical Medicine & Rehabilitation (ZT, RLM, YZ), Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China (YW); Translational Musculoskeletal Research Center (TMRC), Corporal Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, Pennsylvania (SEG, RLM, YZ); and Department of Orthopaedics/Sports Medicine and Joint Surgery, First Affiliated Hospital, China Medical University, Shenyang, Liaoning, China (LY). All correspondence should be addressed to: Yejia Zhang, MD, PhD, Department of Physical Medicine & Rehabilitation, Perelman School of Medicine, University of Pennsylvania, 1800 Lombard St, 1st Floor, Philadelphia, PA 19146. This study was supported in part by research grants to YZ from the Department of Veterans Affairs Healthcare Network, a Penn Center for Musculoskeletal Disorders (PCMD) pilot grant (P30-AR050950-10 Pilot), and a grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS, R21 AR071623). The biomechanics and histology core facilities have been supported by a grant to the PCMD (P30AR069619). This work was also supported in part by research grants to LQ from the NIH (NIAMS R01AR066098 and R01DK095803). All animal use in this study was reviewed and approved by the Institutional Animal Care and Use Committee (IACUC) at the University of Pennsylvania, Philadelphia, PA. All authors approved the final version of the manuscript submitted. Yulong Wei, Robert J. Tower, and Lutian Yao are in training. Financial disclosure statements have been obtained, and no conflicts of interest have been reported by the authors or by any individuals in control of the content of this article. American Journal of Physical Medicine & Rehabilitation 100(5):p 450-457, May 2021. | DOI: 10.1097/PHM.0000000000001575 Buy Metrics Abstract Objective The aim was to identify the source of cells within the center of the abnormal fibrocartilage tissue of the degenerative intervertebral disc after injury. Design Cross-breeding of mice with an inducible type II promoter collagen construct (Col2CreER) to Rosa26-TdTomato mice has been shown to result in Cre-recombinase activity and Tomato expression in inner annulus fibrosus cells after tamoxifen injection. To investigate the role of the inner annulus fibrosus in the intervertebral disc injury response, tail intervertebral discs of Col2CreER/tdTomato mice were punctured with a needle and examined 1–4 wks after injury. N-cadherin was examined by immunostaining. Results After the injury, the fibrocartilage in the degenerative intervertebral disc consisted of residual diseased nucleus pulposus cells and encroaching inner annulus fibrosus cells. The residual nucleus pulposus cells had lost their epithelial cell–like morphology and instead became oval shaped, with reduced adhesion to neighboring nucleus pulposus cells. This change in cellular morphology coincided with a loss of N-cadherin, which contributes to maintenance of healthy nucleus pulposus cell morphology. As expected, injured tail intervertebral discs showed reduced compressive properties as determined by biomechanical assessments. Conclusions The cellular composition of the degenerative intervertebral disc has been defined here, which is an important step in developing future treatments. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.