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Collagen profiling of ligamentum flavum in patients with lumbar spinal canal stenosis
Authors:Hiroki Takeda  Sota Nagai  Daiki Ikeda  Shinjiro Kaneko  Takashi Tsuji  Nobuyuki Fujita
Affiliation:1. Department of Orthopaedic Surgery, School of Medicine, Fujita Health University, Aichi, Japan;2. Department of Spine and Spinal Cord, Fujita Health University, Aichi, Japan;3. Department of Orthopaedic Surgery, National Hospital Organization Tokyo Medical Center, Tokyo, Japan;1. Department of Orthopaedic Surgery, Nihon University Itabashi Hospital, 30-1 Oyaguchikamimati, Itabashi-ku, Tokyo, 173-8610, Japan;2. Department of Orthopaedic Surgery, Sonoda Medical Institute Tokyo Spine Center, 2-5-10 Ikohoncyo Adati-ku, Tokyo, 121-0807, Japan;1. Department of Orthopaedic Surgery, Iwate Prefectural Central Hospital, 1-4-1 Ueda, Morioka 020-0066, Japan;2. Department of Orthopaedic Surgery, Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan;3. Department of Orthopaedic Surgery, Matsuda Hospital, 17-1 Sanezawa Tatutayashiki, Izumi-ku, Sendai 981-3217, Japan;4. Department of Orthopaedic Surgery, Miyagi South Medical Center, 38-1 Aza-nishi, Ogawara, Shibata-gun, Sendai 989-1253, Japan;5. Department of Orthopaedic Surgery, JR Sendai Hospital, 131 Itsutsubashi, Aoba-ku, Sendai 980-8508, Japan;1. Department of Rehabilitation Medicine, Faculty of Medicine, The University of Tokyo, Tokyo, Japan;2. Department of Orthopaedic Surgery, Faculty of Medicine, The University of Tokyo, Tokyo, Japan;3. Department of Health Services Research, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan;4. Department of Clinical Epidemiology and Health Economics, School of Public Health, The University of Tokyo, Tokyo, Japan;5. Department of Health Policy and Informatics, Tokyo Medical and Dental University Graduate school of Medicine, Tokyo, Japan;1. Department of Orthopaedic Surgery, School of Medicine, Keio University, 35 Shinano-machi, Shinjuku, Tokyo, 160-8582, Japan;2. Aiko Orthopaedic Surgery, 1221 Jinmyo, Okehazama, Midori-ku, Nagoya, Aichi, 458-0919, Japan;3. Institute for Integrated Sports Medicine, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo, 160-8582, Japan;1. Department of Orthopedics, Sihong People''s Hospital, Suqian, Jiangsu, 223900, PR China;2. Center for Genetic Epidemiology and Genomics, School of Public Health, Medical College of Soochow University, Suzhou, Jiangsu, 215123, PR China;3. Collaborative Innovation Center of Clinical Immunology Between Soochow University and Sihong People''s Hospital, Jiangsu, PR China;4. Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Soochow University, Suzhou, Jiangsu, 215123, PR China;1. Department of Othopaedic and Spine Surgery, Fukuoka Children''s Hospital, 5-1-1 Kashii Teriha, Higashi-ku, Fukuoka 812-0017, Japan;2. Department of Othopaedic Surgery, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan;3. Department of Othopaedic Surgery, Saga Handicapped Children''s Hospital, 2215-27 Kinryu, Kinryu-machi, Saga 849-0906, Japan
Abstract:BackgroundAlthough several causes of ligamentum flavum (LF) hypertrophy have been identified, the pathomechanisms underlying LF hypertrophy are not fully understood. Because collagen fibers are essential for the maintenance of LF tissues, characterization of the collagen composition of hypertrophied LF may help to elucidate the pathology of lumbar spinal canal stenosis (LCS). This study aimed to determine the association between the collagen composition and LF hypertrophy.MethodsLF tissues were collected from 23 patients who underwent spinal decompression surgery for lumbar disorders. The cross-sectional area of LF was measured using the axial images of lumbar MRI. The expression of each collagen in human surgical samples was evaluated by real-time RT-PCR and immunohistochemical analysis. To investigate the impact of inflammatory cytokines on the expression of each collagen, we treated primary human LF cells with TNF-α or IL-1β.ResultsReal-time RT-PCR analysis and immunohistochemistry showed that of the 28 types of collagen, collagen type I, III, V, VI, VIII were highly expressed regardless of LF hypertrophy. In addition, we found the moderate correlation between the cross-sectional area of LF and the mRNA expression level of collagen type I, III, and VI. In vitro analysis showed that the mRNA expression of collagen type I, III, V, VI, and VIII was up-regulated by treatment with TNF-α and with IL-1β.ConclusionOur results suggested that collagen type I, III, V, VI, and VIII were the main components of the LF extracellular matrix and that collagen type I, III, and VI may serve as useful markers of LF hypertrophy. These findings may contribute to the future development of diagnostic and treatment modalities for LF hypertrophy and even LCS.
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