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Subchondral Bone Fragility With Meniscal Tear Accelerates And Parathyroid Hormone Decelerates Articular Cartilage Degeneration In Rat Osteoarthritis Model
Yugo Morita, H. Ito, Masahiro Ishikawa, T. Fujii, M. Furu, M. Azukizawa, A. Okahata, T. Tomizawa, S. Kuriyama, S. Nakamura, K. Nishitani, H. Yoshitomi, S. Matsuda
Published 2018 · Medicine
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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.
This paper references
Computational biomechanics of articular cartilage of human knee joint: effect of osteochondral defects.
R. Shirazi (2009)
Meniscal tears: The effect of meniscectomy and of repair on intraarticular contact areas and stress in the human knee
M. Baratz (1986)
Acce pt e d Artic le 38
Subchondral bone microstructural damage by increased remodelling aggravates experimental osteoarthritis preceded by osteoporosis
M. Bellido (2010)
Synovial mast cells: role in acute and chronic arthritis
P. Nigrovic (2007)
An update review of cellular mechanisms conferring the indirect and direct effects of estrogen on articular cartilage
L. Tankó (2008)
changes in the rat anterior cruciate ligament transection and meniscec - tomized models of osteoarthritis
H Aagaard (1999)
Efficacy of zoledronic acid in treatment of teoarthritis is dependent on the disease progression stage in rat medial meniscal tear model
Degang Yu (2012)
Acce pt e d Artic le
PTH‐enhanced structural allograft healing is associated with decreased angiopoietin‐2–mediated arteriogenesis, mast cell accumulation, and fibrosis
Robinder S. Dhillon (2013)
Transcriptional regulation of endochondral ossification by HIF-2α during skeletal growth and osteoarthritis development
T. Saito (2010)
Three-Times-Weekly Administration of Teriparatide Improves Vertebral and Peripheral Bone Density, Microarchitecture, and Mechanical Properties Without Accelerating Bone Resorption in Ovariectomized Rats
R. Takao-Kawabata (2015)
Of Mice . . .
S. Simpson (2004)
Randomized Teriparatide [human parathyroid hormone (PTH) 1-34] Once-Weekly Efficacy Research (TOWER) trial for examining the reduction in new vertebral fractures in subjects with primary osteoporosis and high fracture risk.
T. Nakamura (2012)
Exercise intervention increases expression of bone morphogenetic proteins and prevents the progression of cartilage-subchondral bone lesions in a post-traumatic rat knee model.
H. Iijima (2016)
Effects of short-term gentle treadmill walking on subchondral bone in a rat model of instability-induced osteoarthritis.
H. Iijima (2015)
Effects of short-term gentle treadmill walking on subchondral bone in a rat model of instability-induced osteoarthritis. Osteoarthritis Cartilage 23:1563–1574
H Iijima (2015)
Efficacy and safety of strontium ranelate in the treatment of knee osteoarthritis: results of a double-blind, randomised placebo-controlled trial
J. Reginster (2013)
Destabilization of the medial meniscus leads to subchondral bone defects and site-specific cartilage degeneration in an experimental rat model.
H. Iijima (2014)
The role of subchondral bone remodeling in osteoarthritis: reduction of cartilage degeneration and prevention of osteophyte formation by alendronate in the rat anterior cruciate ligament transection model.
T. Hayami (2004)
Aggravation of ADAMTS and Matrix Metalloproteinase Production and Role of ERK1/2 Pathway in the Interaction of Osteoarthritic Subchondral Bone Osteoblasts and Articular Cartilage Chondrocytes — Possible Pathogenic Role in Osteoarthritis
I. Prasadam (2012)
The OARSI histopathology initiative - recommendations for histological assessments of osteoarthritis in the rat.
N. Gerwin (2010)
Teriparatide Treatment Improves Bone Defect Healing Via Anabolic Effects on New Bone Formation and Non‐Anabolic Effects on Inhibition of Mast Cells in a Murine Cranial Window Model
L. Zhang (2017)
A role for subchondral bone changes in the process of osteoarthritis; a micro-CT study of two canine models
Y. H. Sniekers (2008)
Strontium ranelate reduces cartilage degeneration and subchondral bone remodeling in rat osteoarthritis model
Degang Yu (2013)
Induction of osteoarthritis in the rat by surgical tear of the meniscus: Inhibition of joint damage by a matrix metalloproteinase inhibitor.
M. J. Janusz (2002)
Formic Acid-Sodium Citrate Decalcification and Butyl Alcohol Dehydration of Teeth and Bones for Sectioning in Paraffin
A. Morse (1945)
Subchondral cysts create increased intra-osseous stress in early knee OA: A finite element analysis using simulated lesions.
D. McErlain (2011)
Grading and Staging
Y. Park (2015)
Chondroprotective effect of alendronate in a rabbit model of osteoarthritis
T. Shirai (2011)
Destabilization of the medial meniscus leads to subchondral bone defects and sitespecific cartilage degeneration in an experimental rat model. Osteoarthritis Cartilage 22:1036–1043
H Iijima (2014)
Increased bone formation by prevention of osteoblast apoptosis with parathyroid hormone.
R. Jilka (1999)
Meniscal pathology on MRI increases the risk for both incident and enlarging subchondral bone marrow lesions of the knee: the MOST Study
M. Englund (2010)
Regulation of cyclooxygenase-2 expression in bovine chondrocytes in culture by interleukin 1alpha, tumor necrosis factor-alpha, glucocorticoids, and 17beta-estradiol.
S. Morisset (1998)
Function of the normal meniscus and consequences of meniscal resection
H. Aagaard (1999)
Endochondral ossification signals in cartilage degradation during osteoarthritis progression in experimental mouse models.
H. Kawaguchi (2008)
Mechanical loading enhances the anabolic effects of intermittent parathyroid hormone (1-34) on trabecular and cortical bone in mice.
T. Sugiyama (2008)
17Beta-oestradiol up-regulates the expression of a functional UDP-glucose dehydrogenase in articular chondrocytes: comparison with effects of cytokines and growth factors.
L. Maneix (2008)
Characterization of synovial mast cells in knee osteoarthritis: association with clinical parameters.
B. D. de Lange-Brokaar (2016)
The association of meniscal pathologic changes with cartilage loss in symptomatic knee osteoarthritis.
D. Hunter (2006)
Spatiotemporal Analyses of Osteogenesis and Angiogenesis via Intravital Imaging in Cranial Bone Defect Repair
Chunlan Huang (2015)
Bone marrow lesions predict site-specific cartilage defect development and volume loss: a prospective study in older adults
D. Doré (2010)
Effect of risedronate on joint structure and symptoms of knee osteoarthritis: results of the BRISK randomized, controlled trial [ISRCTN01928173]
T. Spector (2005)
Joint distraction attenuates osteoarthritis by reducing secondary inflammation, cartilage degeneration and subchondral bone aberrant change.
Y. Chen (2015)
PTHrP and Skeletal Development
H. Kronenberg (2006)
Subchondral Bone and Cartilage Disease: A Rediscovered Functional Unit
H. Imhof (2000)
Improved methods for immunohistochemical detection of BrdU in hard tissue.
A. Shimada (2008)
The influence of long-term treadmill exercise on bone mass and articular cartilage in ovariectomized rats
Ting-Kuo Chang (2010)
Osteoarthritis cartilage histopathology: grading and staging.
K. Pritzker (2006)
Contribution of runt-related transcription factor 2 to the pathogenesis of osteoarthritis in mice after induction of knee joint instability.
S. Kamekura (2006)
Subchondral bone as a key target for osteoarthritis treatment.
S. Castañeda (2012)
Identification of the core element responsive to runt-related transcription factor 2 in the promoter of human type X collagen gene.
A. Higashikawa (2009)
Bone turnover and articular cartilage differences localized to subchondral cysts in knees with advanced osteoarthritis.
Y. Chen (2015)
Parathyroid hormone (1-34) prevents cartilage degradation and preserves subchondral bone micro-architecture in guinea pigs with spontaneous osteoarthritis.
J. Yan (2014)
Mechanisms of anabolic therapies for osteoporosis.
E. Canalis (2007)
Characterization of articular cartilage and subchondral bone changes in the rat anterior cruciate ligament transection and meniscectomized models of osteoarthritis.
T. Hayami (2006)
Efficacy and safety of strontium ranelate in the treatment of knee osteoarthritis: results of a double-blind, randomised placebocontrolled trial
JY Reginster (2013)
Improving subchondral bone integrity reduces progression of cartilage damage in experimental osteoarthritis preceded by osteoporosis.
M. Bellido (2011)
Osteoarthritis development in novel experimental mouse models induced by knee joint instability.
S. Kamekura (2005)
Parathyroid hormone(1-34) exhibits more comprehensive effects than celecoxib in cartilage metabolism and maintaining subchondral bone micro-architecture in meniscectomized guinea pigs.
M-W Dai (2016)
Characteriza - tion of articular cartilage and subchondral
T Hayami (2006)
Teriparatide as a Chondroregenerative Therapy for Injury-Induced Osteoarthritis
E. Sampson (2011)
Opposite bone remodeling effects of teriparatide and alendronate in increasing bone mass.
M. Mcclung (2005)
Mast cells in the synovium and synovial fluid in osteoarthritis.
G. Dean (1993)
The epidemiology of osteoarthritis.
V. L. Johnson (2014)
17 Beta - oestradiol upregulates the expression of a functional UDP - glucose dehydrogenase in articular chondrocytes : comparison with effects of cytokines and growth factors
L Maneix (2008)
Meniscal damage associated with increased local subchondral bone mineral density: a Framingham study.
G. Lo (2008)
Increased osteoblast and osteoclast indices in individuals with systemic mastocytosis
S. Seitz (2013)
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