Yulong Wei1, Zuozhen Tian, Robert J Tower, Sarah E Gullbrand, Lutian Yao, Snehal S Shetye, Robert L Mauck, Ling Qin, Yejia Zhang. 1. 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).
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.
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.
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