RRC ID 61927
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)