Exercise intervention increases expression of bone morphogenetic proteins and prevents the progression of cartilage-subchondral bone lesions in a post-traumatic rat knee model

Iijima, Hirotaka; Aoyama, Tomoki; Ito, Akira; Tajino, Junichi; Yamaguchi, Satoshi; Nagai, Masaya; Kiyan, W.; Zhang, X.; Kuroki, Hiroshi

doi:10.1016/j.joca.2016.01.006

Cited by 44 publications

(46 citation statements)

References 47 publications

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“…Among the BMP family, BMP-2, -4, -6, and -7 have been shown to accelerate chondrogenic and osteogenic differentiation of progenitor cells in vitro 31 and enhance cartilage-specific matrix production both in vitro and in vivo 16,32 . Since the expression of these in articular cartilage and SB is sensitive to mechanical loading 18,19 , we contemplated whether physiological moderate exercise would induce the expression of BMPs in the articular cartilage and SB, and thereby delay PTOA development. In this study, we found that moderate exercise did increase superficial zone BMPs expression, as well as their BMPR2, pSmad-5, and Id-1, which corresponded to prevention of proteoglycan loss and maintenance of the stiffness of articular cartilage.…”

Section: Discussionmentioning

confidence: 99%

“…BMP enhances cartilage matrix synthesis as well as osteogenic activity of bone cells in vivo 16,17 , suggesting that BMPs may contribute to the intrinsic repair capacity of damaged cartilage-bone units. Recent studies showed that messenger RNA expression of BMPs in the cartilage-bone unit was upregulated by moderate exercise in vivo 18 , and moderate exercise increased expression of BMPs, which coincides with the prevention of the progression of PTOA in the instability-induced PTOA knee 19 . However, their function is not yet clear; further investigation of the role of BMPs in the protection against cartilage-bone damage and their interaction with the dose-dependent response of exercise intervention is warranted.…”

Section: Introductionmentioning

confidence: 97%

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

Iijima

Ito

Nagai

et al. 2017

Osteoarthritis and Cartilage

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 97%

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

Iijima

Ito

Nagai

et al. 2017

Osteoarthritis and Cartilage

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“…Moderate mechanical loading could maintain the integrity of the cartilage and prevent the progression of cartilage-subchondral bone lesions [23, 24]. However, overuse of joints may result in cartilage degradation [15, 16, 25].…”

Section: Discussionmentioning

confidence: 99%

Morphological and Microstructural Alterations of the Articular Cartilage and Bones during Treadmill Exercises with Different Additional Weight-Bearing Levels

Gao

Fang

Gong

et al. 2017

Journal of Healthcare Engineering

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The aim of this study was to investigate the morphological and microstructural alterations of the articular cartilage and bones during treadmill exercises with different exercise intensities. Sixty 5-week-old female rats were randomly divided into 10 groups: five additional weight-bearing groups (WBx) and five additional weight-bearing with treadmill exercise groups (EBx), which were subjected to additional weight bearing of x% (x = 0, 5, 12, 19, and 26) of the corresponding body weight of each rat for 15 min/day. After 8 weeks of experiment, the rats were humanely sacrificed and their bilateral intact knee joints were harvested. Morphological analysis of the cartilages and microcomputed tomography evaluation of bones were subsequently performed. Results showed that increased additional weight bearing may lead to cartilage damage. No significant difference was observed among the subchondral cortical thicknesses of the groups. The microstructure of subchondral trabecular bone of 12% and 19% additional weight-bearing groups was significantly improved; however, the WB26 and EB26 groups showed low bone mineral density and bone volume fraction as well as high structure model index. In conclusion, effects of treadmill exercise on joints may be associated with different additional weight-bearing levels, and exercise intensities during joint growth and maturation should be selected reasonably.

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“…The sections were incubated with a polymeric secondary antibody (SuperPicTure Polymer Detection Kit, Invitrogen Co.) and diaminobenzidine solution, followed by counterstaining with hematoxylin. We defined the expression of MMP‐13 and type X collagen in the articular chondrocytes as the percentage of MMP‐13‐positive chondrocytes and type X collagen‐positive chondrocytes observed within the middle region of the medial tibia with a mediolateral width of 0.5 mm . The images were analyzed using BZ‐analyzer (Keyence Co.).…”

Section: Methodsmentioning

confidence: 99%

Subchondral bone fragility with meniscal tear accelerates and parathyroid hormone decelerates articular cartilage degeneration in rat osteoarthritis model

Morita

Ito

Ishikawa

et al. 2018

Journal Orthopaedic Research

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The aims of this study were to investigate the influence of subchondral bone fragility (SBF) on the progression of the knee osteoarthritis by using a novel rat model, and to examine the preventive effect of parathyroid hormone (PTH) on cartilage degeneration. First, 40 rats were assigned to the following four groups: Sham, SBF, Medial meniscal tear (MMT), and MMT + SBF groups. In SBF and MMT + SBF groups, we induced SBF by microdrilling the subchondral bone. Second, 10 additional rats were randomly assigned to the following two groups: MMT + SBF + saline and MMT + SBF + PTH groups. Osteoarthritic changes in the articular cartilage and subchondral bone were evaluated using safranin-O/fast green staining, matrix metalloproteinase-13 (MMP-13), and type X collagen immunohistochemistry, toluidine blue staining, and micro-CT scanning. The combination of SBF and meniscal tear increased the number of mast cells in the subchondral bone, and led to the abnormal subchondral bone microarchitecture, such as abnormally decreased trabecular number and increased trabecular thickness, compared with meniscal tear alone. Moreover, SBF with meniscal tear enhanced articular cartilage degeneration and increased the expression of MMP-13 and type X collagen, compared with meniscal tear alone. The administration of PTH decreased the number of mast cells in the subchondral bone and improved the microstructural parameters of the subchondral bone, and delayed the progression of articular cartilage degeneration. These results suggest that SBF is one of the factors underlying the osteoarthritis development, especially in knees with traumatic osteoarthritis, and that the administration of PTH is a potential therapeutic treatment for preventing OA progression. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1959-1968, 2018.

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Exercise intervention increases expression of bone morphogenetic proteins and prevents the progression of cartilage-subchondral bone lesions in a post-traumatic rat knee model

Cited by 44 publications

References 47 publications

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

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

Morphological and Microstructural Alterations of the Articular Cartilage and Bones during Treadmill Exercises with Different Additional Weight-Bearing Levels

Subchondral bone fragility with meniscal tear accelerates and parathyroid hormone decelerates articular cartilage degeneration in rat osteoarthritis model

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