論文 - 詳細
RRC ID | 61927 |
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著者 | Iijima H, Ito A, Nagai M, Tajino J, Yamaguchi S, Kiyan W, Nakahata A, Zhang J, Wang T, Aoyama T, Nishitani K, Kuroki H. |
タイトル | Physiological exercise loading suppresses post-traumatic osteoarthritis progression via an increase in bone morphogenetic proteins expression in an experimental rat knee model. |
ジャーナル | Osteoarthritis Cartilage |
Abstract |
OBJECTIVE:To evaluate the dose-response relationship of exercise loading in the cartilage-subchondral bone (SB) unit in surgically-induced post-traumatic osteoarthritis (PTOA) of the knee. DESIGN:Destabilized medial meniscus (DMM) surgery was performed on the right knee of 12-week-old male Wistar rats, and sham surgery was performed on the contralateral knee. Four weeks after the surgery, the animals were subjected to moderate (12 m/min) or intense (21 m/min) treadmill exercises for 30 min/day, 5 days/week for 4 weeks. PTOA development in articular cartilage and SB was examined using histological and immunohistochemical analyses, micro-computed tomography (micro-CT) analysis, and biomechanical testing at 8 weeks after surgery. Gremlin-1 was injected to determine the role of bone morphogenetic protein (BMP) signaling on PTOA development following moderate exercise. RESULTS:Moderate exercise increased BMP-2, BMP-4, BMP-6, BMP receptor 2, pSmad-5, and inhibitor of DNA binding protein-1 expression in the superficial zone chondrocytes and suppressed cartilage degeneration, osteophyte growth, SB damage, and osteoclast-mediated SB resorption. However, intense exercise had little effect on BMP expression and even caused progression of these osteoarthritis (OA) changes. Gremlin-1 injection following moderate exercise caused progression of the PTOA development down to the level of the non-exercise DMM-operated knee. CONCLUSIONS:Exercise regulated cartilage-SB PTOA development in DMM-operated knees in a dose-dependent manner. Our findings shed light on the important role of BMP expression in superficial zone chondrocytes in attenuation of PTOA development following physiological exercise loading. Further studies to support a mechanism by which BMPs would be beneficial in preventing PTOA progression are warranted. |
巻・号 | 25(6) |
ページ | 964-975 |
公開日 | 2017-6-1 |
DOI | 10.1016/j.joca.2016.12.008 |
PII | S1063-4584(16)30468-X |
PMID | 27965139 |
MeSH | Animals Bone Morphogenetic Protein 2 / drug effects Bone Morphogenetic Protein 2 / metabolism Bone Morphogenetic Protein 4 / drug effects Bone Morphogenetic Protein 4 / metabolism Bone Morphogenetic Protein 6 / drug effects Bone Morphogenetic Protein 6 / metabolism Bone Morphogenetic Protein Receptors, Type II / drug effects Bone Morphogenetic Protein Receptors, Type II / metabolism Bone Morphogenetic Proteins / drug effects Bone Morphogenetic Proteins / metabolism* Cartilage, Articular / drug effects Cartilage, Articular / metabolism* Chondrocytes / drug effects Chondrocytes / metabolism* Cytokines Inhibitor of Differentiation Protein 1 Knee Joint / drug effects Knee Joint / metabolism* Male Osteoarthritis, Knee / etiology Osteoarthritis, Knee / metabolism* Physical Conditioning, Animal* Proteins / pharmacology Rats Rats, Wistar Smad5 Protein / drug effects Smad5 Protein / metabolism Tibial Meniscus Injuries / complications Tibial Meniscus Injuries / metabolism Weight-Bearing* |
IF | 4.793 |
リソース情報 | |
ヒト・動物細胞 | MC3T3-E1(RCB1126) |