Yi-Jie Kuo1, Lien-Chen Wu2, Jui-Sheng Sun3, Ming-Hong Chen4, Man-Ger Sun5, Yang-Hwei Tsuang6. 1. Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan, ROC. 2. Graduate Institute of Biomedical Engineering, National Taiwan University, Taipei, Taiwan, ROC. 3. Department of Orthopedic Surgery, School of Medicine, College of Medicine, National Taiwan University, 1, Jen-Ai Road, Section 1, Taipei 10051, Taiwan, ROC; Department of Orthopedic Surgery, National Taiwan University Hospital Hsin-Chu Branch, No.25, Lane 442, Sec. 1, Jingguo Rd., Hsinchu City 30059, Taiwan, ROC. Electronic address: drjssun@gmail.com. 4. Department of Surgery, National Taiwan University Hospital Hsin-Chu Branch, Hsinchu City, Taiwan, ROC. 5. Department of Biology, Western University, London, ON N6A 5C1, Canada. 6. Department of Orthopedic Surgery, Taipei Medical University-Shuang-Ho Hospital, No.291, Jhongjheng Rd., Jhonghe City, New Taipei 23561, Taiwan, ROC. Electronic address: tsuangyh@gmail.com.
Abstract
BACKGROUND: Un-physiological loads play an important role in the degenerative process of inter-vertebral discs (IVD). In this study, we used an in vitro and in vivo rat model to investigate the mechanism of nucleus pulposus (NP) cells apoptosis induced by mechanical stress. METHODS: Static compressive load to IVDs of rat tails was used as the in vivo model. For the in vitro model, NP cells were tested under the physiological and un-physiological loading. For histological examination, apoptotic index study, and apoptotic gene expression, we also selected cytokines [bone morphogenetic protein (BMP)-2/7, insulin-like growth factor (IGF)-1, platelet-derived growth factor (PDGF)] to be analyzed. RESULTS: Under mechanical loading, cellular density was significantly decreased, but there was an increase of TUNEL positive cells and apoptosis index. In a dose-dependent manner; the necrosis became apparent in the un-physiologic strain. The selected cytokines (BMP-2/7, IGF-1, PDGF) can significantly reduce the percentage of apoptotic and necrotic cells. CONCLUSIONS: We conclude that the intrinsic (mitochondrial) apoptotic pathway plays an important role in the compressive load-induced apoptosis of NP cells. Combination therapy reducing the mechanical load and selected cytokines (BMP-2/7, IGF-1 and PDGF) may have considerable promise in the treatment of spine disc degeneration.
BACKGROUND: Un-physiological loads play an important role in the degenerative process of inter-vertebral discs (IVD). In this study, we used an in vitro and in vivo rat model to investigate the mechanism of nucleus pulposus (NP) cells apoptosis induced by mechanical stress. METHODS: Static compressive load to IVDs of rat tails was used as the in vivo model. For the in vitro model, NP cells were tested under the physiological and un-physiological loading. For histological examination, apoptotic index study, and apoptotic gene expression, we also selected cytokines [bone morphogenetic protein (BMP)-2/7, insulin-like growth factor (IGF)-1, platelet-derived growth factor (PDGF)] to be analyzed. RESULTS: Under mechanical loading, cellular density was significantly decreased, but there was an increase of TUNEL positive cells and apoptosis index. In a dose-dependent manner; the necrosis became apparent in the un-physiologic strain. The selected cytokines (BMP-2/7, IGF-1, PDGF) can significantly reduce the percentage of apoptotic and necrotic cells. CONCLUSIONS: We conclude that the intrinsic (mitochondrial) apoptotic pathway plays an important role in the compressive load-induced apoptosis of NP cells. Combination therapy reducing the mechanical load and selected cytokines (BMP-2/7, IGF-1 and PDGF) may have considerable promise in the treatment of spine disc degeneration.
Authors: Olga Krupkova; Junichi Handa; Marian Hlavna; Juergen Klasen; Caroline Ospelt; Stephen John Ferguson; Karin Wuertz-Kozak Journal: Oxid Med Cell Longev Date: 2016-03-28 Impact factor: 6.543