Mechanical Stress-Induced Apoptosis of Endplate Chondrocytes in Organ-Cultured Mouse Intervertebral Discs

作者：Kenta Ariga, Kazuo Yonenobu, Takanobu Nakase, Noboru Hosono, Shinya Okuda, Wenxiang Meng, Yuichi Tamura, Hideki Yoshikawa · 发表于：Spine · 年份：2003 · DOI：10.1097/01.brs.0000076915.55939.e3 · 被引用次数：143 · 研究领域：Spine and Intervertebral Disc Pathology、Cervical and Thoracic Myelopathy、Musculoskeletal pain and rehabilitation

STUDY DESIGN: Various amounts of static mechanical load were applied to mouse intervertebral discs in organ cultures. The apoptosis then was examined using nick end labeling. Two mitogen-activated protein kinase (MAPK) inhibitors were added to the medium. OBJECTIVES: To establish an experimental model for detecting factors regulating chondrocyte apoptosis induced by mechanical stress, and to determine the role of MAPK and p38 in the stress-induced apoptotic pathway of endplate chondrocytes. SUMMARY OF BACKGROUND DATA: The cause of degenerative change in the cartilaginous endplate (CEP) remains unclear. The authors' previous findings using a mouse model suggested that apoptosis in the cartilaginous endplate may play a role in intervertebral disc degeneration, and that mechanical stress may induce apoptosis. If apoptosis of endplate chondrocytes is involved in the cascade of intervertebral disc degeneration, then how apoptosis is induced by mechanical stress should be important in preventing disc degeneration. However, the mechanism of apoptosis induced by mechanical stress remains unclear. METHODS: Mouse coccygeal discs were harvested and organ cultured. Various static compression loads (0, 0.2, 0.4, 0.8, and 1.0 MPa) were applied on intervertebral discs placed in culture bottles for 24 hours. Paraffin-embedded sections of the harvested discs were stained using Safranin-O and the nick end labeling procedure. The apoptotic cells were counted in the cartilaginous endplate and ju...