Subchondral bone turnover, but not bone volume, is increased in early stage osteoarthritic lesions in the human hip joint

Klose-Jensen, Rasmus; Hartlev, Louise Brøndt; Boel, Lene Warner Thorup; Laursen, Mogens Berg; Stengaard‐Pedersen, Kristian; Keller, Kresten Krarup; Hauge, Ellen‐Margrethe

doi:10.1016/j.joca.2015.06.001

Cited by 49 publications

(62 citation statements)

References 44 publications

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“…We further demonstrated that osteoclast number also increased in p21 −/− mice. Previous studies suggested that a thickening of the subchondral bone plate occurs as a primary fundamental change in subchondral bone in OA, and another study demonstrated that thinning of the subchondral bone occurred before cartilage destruction . These studies suggested that subchondral bone plays a critical role in OA progression.…”

Section: Discussionmentioning

confidence: 91%

Cyclin-Dependent Kinase Inhibitor-1-Deficient Mice are Susceptible to Osteoarthritis Associated with Enhanced Inflammation

Kihara

Hayashi

Hashimoto

et al. 2017

Journal of Bone and Mineral Research

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Osteoarthritis (OA) is a multifactorial disease, and recent data suggested that cell cycle-related proteins play a role in OA pathology. Cyclin-dependent kinase (CDK) inhibitor 1 (p21) regulates activation of other CDKs, and recently, we reported that p21 deficiency induced susceptibility to OA induced by destabilization of the medial meniscus (DMM) surgery through STAT3-signaling activation. However, the mechanisms associated with why p21 deficiency led to susceptibility to OA by the STAT3 pathway remain unknown. Therefore, we focused on joint inflammation to determine the mechanisms associated with p21 function during in vitro and in vivo OA progression. p21-knockout (p21 ) mice were used to develop an in vivo OA model, and C57BL/6 (p21 ) mice with the same background as the p21 mice were used as controls. Morphogenic changes were measured using micro-CT, IL-1β serum levels were detected by ELISA, and histological or immunohistological analyses were performed. Our results indicated that p21-deficient DMM-model mice exhibited significant subchondral bone destruction and cartilage degradation compared with wild-type mice. Immunohistochemistry results revealed p21 mice susceptibility to OA changes accompanied by macrophage infiltration and enhanced MMP-3 and MMP-13 expression through IL-1β-induced NF-κB signaling. p21 mice also showed subchondral bone destruction according to micro-CT analysis, and cathepsin K staining revealed increased numbers of osteoclasts. Furthermore, p21 mice displayed increased serum IL-1β levels, and isolated chondrocytes from p21 mice indicated elevated MMP-3 and MMP-13 expression with phosphorylation of IκB kinase complex in response to IL-1β stimulation, whereas treatment with a specific p-IκB kinase inhibitor attenuated MMP-3 and MMP-13 expression. Our results indicated that p21-deficient DMM mice were susceptible to alterations in OA phenotype, including enhanced osteoclast expression, macrophage infiltration, and MMP expression through IL-1β-induced NF-κB signaling, suggesting that p21 regulation may constitute a possible therapeutic strategy for OA treatment. © 2017 American Society for Bone and Mineral Research.

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Section: Discussionmentioning

confidence: 91%

Cyclin-Dependent Kinase Inhibitor-1-Deficient Mice are Susceptible to Osteoarthritis Associated with Enhanced Inflammation

Kihara

Hayashi

Hashimoto

et al. 2017

Journal of Bone and Mineral Research

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“…Some studies have previously suggested that a thickening of the growth plate is occurring as a primary fundamental subchondral bone change in OA (147). It has also been demonstrated in animal studies that thinning of the subchondral bone occurred before cartilage damage was detected, suggesting that bone turnover may be increased in the early stages of OA (148). Surely, changes to subchondral bone in the progressive stages of OA are characterized by extensive remodeling of the trabeculae, formation of new bone below new cartilage (osteophytes), and the development of subchondral bone cysts (SBC) (149)(150)(151).…”

Section: Subchondral Bone Changes In Oamentioning

confidence: 97%

Recent advances in the understanding of molecular mechanisms of cartilage degeneration, synovitis and subchondral bone changes in osteoarthritis

Wei

Bai

2016

Connective Tissue Research

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Osteoarthritis (OA), the most common form of degenerative joint disease, is linked to high morbidity. It is predicted to be the single greatest cause of disability in the general population by 2030. The development of disease-modifying therapy for OA currently face great obstacle mainly because the onset and development of the disease involve complex molecular mechanisms. In this review, we will comprehensively summarize biological and pathological mechanisms of three key aspects: degeneration of articular cartilage, synovial immunopathogenesis, and changes in subchondral bone. For each tissue, we will focus on the molecular receptors, cytokines, peptidases, related cell, and signal pathways. Agents that specifically block mechanisms involved in synovial inflammation, degeneration of articular cartilage, and subchondral bone remodeling can potentially be exploited to produce targeted therapy for OA. Such new comprehensive agents will benefit affected patients and bring exciting new hope for the treatment of OA.

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“…7,8 The presence and extent of facet joint OA associate with LBP, independent from disc height narrowing, in elderly individuals. 9 Enhanced subchondral bone turnover is a key pathomechanism in idiopathic OA of the hip 10 and knee 11 and leads to subchondral bone sclerosis in advanced disease stages. Pharmacological inhibition of subchondral bone remodeling or surgical restoration of joint biomechanics can revert subchondral bone sclerosis and have demonstrated clinical efficacy in OA.…”

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confidence: 99%

Characterization of subchondral bone histopathology of facet joint osteoarthritis in lumbar spinal stenosis

Netzer

Urech

Hügle

et al. 2016

Journal Orthopaedic Research

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Facet joint osteoarthritis may be a cause of low back pain in degenerative spine diseases including lumbar spinal stenosis. Subchondral bone is regarded as a potential therapeutic target for osteoarthritis treatment. The goal of this study was to characterize subchondral bone histopathology in osteoarthritic facet joints from lumbar spinal stenosis patients. Fifteen patients with degenerative spinal stenosis scheduled for transforaminal lumbar interbody fusion surgery were recruited for this study. Osteoarthritis severity was graded on T1- and T2-weighted MRI images using Weishaupt scoring system. Dissected osteoarthritic facet joints were subjected to histological and immunohistochemistry analyses to study relative abundance of osteoblast, osteoclasts, and macrophages using van Gieson's, tartrate-resistant acid phosphatase and CD68-antibody staining, respectively. Presence of nerve fibers was evaluated by PGP9.5-antibody staining. Differential bone histopathology, independent from radiological osteoarthritis grade, was observed in facet joints. Extensive de novo bone formation was found in subchondral bone tissues of eight of fifteen specimens. Regions of bone formation showed high abundance of blood vessels and CD68-positive macrophages, but were devoid of multinucleated osteoclasts. Additional pathological changes in subchondral marrow spaces, including inflammatory infiltration and enhanced osteoclast activity, were characterized by macrophage-rich tissues. PGP9.5-positive nerve fibers were detected near arterioles, but not in regions displaying bone pathology. Individual histopathological parameters did not associate with clinical features or radiological osteoarthritis severity. Subchondral bone histopathology of facet joint osteoarthritis in lumbar spinal stenosis is characterized by marrow infiltration by macrophage-rich tissues and enhanced de novo bone formation. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1475-1480, 2016.

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Subchondral bone turnover, but not bone volume, is increased in early stage osteoarthritic lesions in the human hip joint

Cited by 49 publications

References 44 publications

Cyclin-Dependent Kinase Inhibitor-1-Deficient Mice are Susceptible to Osteoarthritis Associated with Enhanced Inflammation

Cyclin-Dependent Kinase Inhibitor-1-Deficient Mice are Susceptible to Osteoarthritis Associated with Enhanced Inflammation

Recent advances in the understanding of molecular mechanisms of cartilage degeneration, synovitis and subchondral bone changes in osteoarthritis

Characterization of subchondral bone histopathology of facet joint osteoarthritis in lumbar spinal stenosis

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