Physiological exercise loading suppresses post-traumatic osteoarthritis progression via an increase in bone morphogenetic proteins expression in an experimental rat knee model

• Published in: Osteoarthritis and cartilage Vol. 25; no. 6; pp. 964 - 975
• Main Authors: Iijima, H, Ito, A, Nagai, M, Tajino, J, Yamaguchi, S, Kiyan, W, Nakahata, A, Zhang, J, Wang, T, Aoyama, T, Nishitani, K, Kuroki, H
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.06.2017
• Subjects: Animals; Bone micro-CT; Bone morphogenetic protein; 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; Cartilage, Articular - drug effects; Cartilage, Articular - metabolism; Chondrocytes - drug effects; Chondrocytes - metabolism; Cytokines; Exercise; Gremlin-1; Inhibitor of Differentiation Protein 1; Knee Joint - drug effects; Knee Joint - metabolism; Male; Osteoarthritis; Osteoarthritis, Knee - etiology; Osteoarthritis, Knee - metabolism; Physical Conditioning, Animal; Proteins - pharmacology; Rats; Rats, Wistar; Rheumatology; Smad5 Protein - drug effects; Smad5 Protein - metabolism; Tibial Meniscus Injuries - complications; Tibial Meniscus Injuries - metabolism; Weight-Bearing; Cartilage; Exercise; Bone morphogenetic protein; Gremlin-1; Bone micro-CT; Osteoarthritis
• ISSN: 1063-4584; 1522-9653
• DOI: 10.1016/j.joca.2016.12.008

Summary 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.