Evolving concepts of new bone formation in axial spondyloarthritis: Insights from animal models and human studies

2017 ◽  
Vol 31 (6) ◽  
pp. 877-886 ◽  
Author(s):  
Rik J. Lories ◽  
Nigil Haroon
Keyword(s):  
Animal Models ◽  
Bone Formation ◽  
Axial Spondyloarthritis ◽  
Human Studies ◽  
New Bone Formation

scholarly journals Bone Morphogenetic Proteins, Carriers, and Animal Models in the Development of Novel Bone Regenerative Therapies

Materials ◽  
2021 ◽  
Vol 14 (13) ◽  
pp. 3513
Author(s):  
Nikola Stokovic ◽  
Natalia Ivanjko ◽  
Drazen Maticic ◽  
Frank P. Luyten ◽  
Slobodan Vukicevic
Keyword(s):  
Animal Models ◽  
Bone Formation ◽  
Bone Morphogenetic Proteins ◽  
Animal Experiments ◽  
Inorganic Materials ◽  
New Bone Formation ◽  
Segmental Bone ◽  
Posterolateral Spinal Fusion ◽  
Regenerative Therapies ◽  
Observation Period

Bone morphogenetic proteins (BMPs) possess a unique ability to induce new bone formation. Numerous preclinical studies have been conducted to develop novel, BMP-based osteoinductive devices for the management of segmental bone defects and posterolateral spinal fusion (PLF). In these studies, BMPs were combined with a broad range of carriers (natural and synthetic polymers, inorganic materials, and their combinations) and tested in various models in mice, rats, rabbits, dogs, sheep, and non-human primates. In this review, we summarized bone regeneration strategies and animal models used for the initial, intermediate, and advanced evaluation of promising therapeutical solutions for new bone formation and repair. Moreover, in this review, we discuss basic aspects to be considered when planning animal experiments, including anatomical characteristics of the species used, appropriate BMP dosing, duration of the observation period, and sample size.

Axial Spondyloarthritis and New Bone Formation

2021 ◽  
Vol 30 (04) ◽  
pp. 311-318
Author(s):  
Uta Syrbe
Keyword(s):  
Bone Formation ◽  
Structural Damage ◽  
Axial Spondyloarthritis ◽  
Clinical Symptoms ◽  
Research Work ◽  
New Bone Formation ◽  
Sacroiliac Joints ◽  
Spine Mobility ◽  
Vertebral Bodies ◽  
Inflammatory Changes

AbstractAxial spondyloarthritis is an inflammatory disease of the axial skeleton. Its pathogenesis is only partly understood. At the beginning, there are inflammatory changes in the sacroiliac joints which are followed by inflammation in vertebral bodies and in facet joints. Low back pain occurring in the morning hours is the dominant clinical symptom. In the early phase, inflammatory changes are detectably by MRI. Inflammation promotes a process of joint remodelling in the sacroiliac joints which leads to erosions, sclerosis and bony bridging, i. e. ankylosis, which are detectable by X-ray. In the spine, vertical osteophytes developing at sites of previous inflammation connect vertebral bodies as syndesmophytes. Additional ossification of longitudinal ligaments contributes to the so-called bamboo spine. Ossification of the spine promotes fixation of a severe kyphosis of the thoracic spine which strongly impairs spine mobility and quality of life. High disease activity seems a prominent risk factor for development of structural damage. However, although NSAIDs improve clinical symptoms, they do not reduce new bone formation. In contrast, TNFα and IL-17 inhibitors seem to retard new bone formation apart from their clinical efficacy. Research work of the last years identified immunological pathways of inflammation. However, the trigger and cellular components of the immune reaction in the bone marrow are still poorly defined. Osteoclasts are involved in the destruction of the subchondral bone, while osteoblasts facilitate new bone formation and cartilage ossification. This review gives an overview about diagnostics and therapy of axSpA and about risk factors for the development of structural damage. Concepts about the immune pathogenesis and joint remodeling in AS are given under recognition of genetic and histopathological studies.

scholarly journals Canada-Denmark MRI scoring system of the spine in patients with axial spondyloarthritis: updated definitions, scoring rules and inter-reader reliability in a multiple reader setting

RMD Open ◽  
2019 ◽  
Vol 5 (2) ◽  
pp. e001057 ◽  
Author(s):  
Simon Krabbe ◽  
Mikkel Østergaard ◽  
Susanne J Pedersen ◽  
Ulrich Weber ◽  
Georg Kröber ◽  
...  
Keyword(s):  
Bone Formation ◽  
Scoring System ◽  
Axial Spondyloarthritis ◽  
Comprehensive Evaluation ◽  
Bone Erosion ◽  
Intraclass Correlation ◽  
New Bone Formation ◽  
Good Reliability ◽  
Single Measure ◽  
Reader Reliability

ObjectiveTo validate the Canada-Denmark (CANDEN) MRI scoring system for the spine in axial spondyloarthritis with updated lesion definitions.MethodsLesion definitions in the CANDEN system were updated and illustrated by a consensus set of reference images. Sagittal spine MRIs of 40 patients with axial spondyloarthritis obtained at baseline and at week 52 after initiation of treatment with the tumour necrosis factor inhibitor golimumab were evaluated in unknown chronology by seven readers blinded to all other data.ResultsCANDEN MRI spine inflammation score had very good reliability for status scores (single-measure intraclass correlation coefficient (ICC) of 21 reader pairs median of 0.91 (IQR 0.88–0.92)) and change scores (ICC 0.88 (0.86–0.92)). CANDEN MRI spine fat score had good to very good reliability for status scores (ICC 0.79 (0.75–0.86)) and moderate to good reliability for detecting change (ICC 0.59 (0.46–0.73)). CANDEN MRI spine bone erosion score and CANDEN MRI spine new bone formation score had slight to moderate reliability for status scores (ICC 0.38 (0.32–0.52) and 0.39 (0.27–0.49), respectively).ConclusionThe CANDEN MRI spine scoring system allows a comprehensive evaluation of inflammation, fat, bone erosion and new bone formation of the spine in patients with axial spondyloarthritis. It demonstrated very good reliability for detecting change in inflammation, moderate to good reliability for detecting change in fat, and slight to moderate reliability for detecting bone erosions and new bone formation. Studies with longer follow-up or patients with more advanced spinal involvement may be needed to reliably detect change in bone erosion and new bone formation scores.Trial registration numberNCT02011386.

Pathology: bone

2016 ◽  
Author(s):  
Rik J. Lories ◽  
Georg Schett
Keyword(s):  
Bone Formation ◽  
Structural Damage ◽  
Axial Spondyloarthritis ◽  
Signalling Pathways ◽  
New Bone Formation ◽  
Different Types ◽  
Significant Burden ◽  
Current Therapies ◽  
Developmental Signalling ◽  
Biomechanical Factors

Axial spondyloarthritis is associated with different types of skeletal damage. Inflammation at the affected sites is linked with both loss of trabecular bone and new bone formation on the cortical side, potentially leading to joint or spine ankylosis. Both aspects of the disease can result in a significant burden for the patient. Bone loss is directly linked to proinflammatory cytokines and activation of osteoclasts. Control of inflammation is therefore the best strategy to prevent loss of bone. The nature of the new bone formation process is less defined. A prominent role for developmental signalling pathways has been proposed. Current therapies have limited or no impact on this process. However, emerging data suggest that early control of disease activity may be part of a window of opportunity to prevent structural damage, as biomechanical factors and instability following inflammation may also play a role.

scholarly journals To move or not to move: the paradoxical effect of physical exercise in axial spondyloarthritis

RMD Open ◽  
2021 ◽  
Vol 7 (1) ◽  
pp. e001480
Author(s):  
Fabio Massimo Perrotta ◽  
Rik Lories ◽  
Ennio Lubrano
Keyword(s):  
Physical Exercise ◽  
Bone Formation ◽  
Axial Spondyloarthritis ◽  
Current Evidence ◽  
Clinical Experiences ◽  
New Bone Formation ◽  
Biomechanical Stress ◽  
Beneficial Effects ◽  
Exercise Programmes

In the last years, new researches focused on the role of biomechanical stress and microdamage in the pathogenesis of inflammatory arthritis and, in particular, in axial spondyloarthritis (axSpA). Animal models showed how entheseal stress and physical exercise could contribute to the development of inflammation and new bone formation at entheseal and articular sites, by activating innate immune system and the release of cytokines. Furthermore, clues of the involvement of biomechanical stress in the development of axSpA are present in clinical experiences. However, rehabilitation and exercise programmes are the cornerstone of treatment for axSpA, reducing disease activity and improving spinal function and quality of life. The concept of mechanical stress as a contributor to disease development and progression represents, potentially, a conceptual challenge for this approach. The aim of this review is to discuss the current evidence on the intriguing contribution of the biomechanical stress to the pathogenesis of inflammation and new bone formation and to evaluate and reflect on the role of exercise in the treatment and in the management of the disease, considering both the beneficial effects and its possible paradoxical action.

New bone formation in axial spondyloarthritis

2013 ◽  
Vol 80 (5) ◽  
pp. 454-458 ◽  
Author(s):  
Daniel Wendling ◽  
Pascal Claudepierre
Keyword(s):  
Bone Formation ◽  
Axial Spondyloarthritis ◽  
New Bone Formation

scholarly journals Tenascin-C-mediated suppression of extracellular matrix adhesion force promotes entheseal new bone formation through activation of Hippo signalling in ankylosing spondylitis

2021 ◽  
pp. annrheumdis-2021-220002
Author(s):  
Zihao Li ◽  
Siwen Chen ◽  
Haowen Cui ◽  
Xiang Li ◽  
Dongying Chen ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Ankylosing Spondylitis ◽  
Animal Models ◽  
Bone Formation ◽  
Rna Sequencing ◽  
Adhesion Force ◽  
Immunofluorescence Staining ◽  
New Bone Formation ◽  
Tenascin C ◽  
Hippo Signalling

ObjectivesThe aim of this study was to identify the role of tenascin-C (TNC) in entheseal new bone formation and to explore the underlying molecular mechanism.MethodsLigament tissue samples were obtained from patients with ankylosing spondylitis (AS) during surgery. Collagen antibody-induced arthritis and DBA/1 models were established to observe entheseal new bone formation. TNC expression was determined by immunohistochemistry staining. Systemic inhibition or genetic ablation of TNC was performed in animal models. Mechanical properties of extracellular matrix (ECM) were measured by atomic force microscopy. Downstream pathway of TNC was analysed by RNA sequencing and confirmed with pharmacological modulation both in vitro and in vivo. Cellular source of TNC was analysed by single-cell RNA sequencing (scRNA-seq) and confirmed by immunofluorescence staining.ResultsTNC was aberrantly upregulated in ligament and entheseal tissues from patients with AS and animal models. TNC inhibition significantly suppressed entheseal new bone formation. Functional assays revealed that TNC promoted new bone formation by enhancing chondrogenic differentiation during endochondral ossification. Mechanistically, TNC suppressed the adhesion force of ECM, resulting in the activation of downstream Hippo/yes-associated protein signalling, which in turn increased the expression of chondrogenic genes. scRNA-seq and immunofluorescence staining further revealed that TNC was majorly secreted by fibroblast-specific protein-1 (FSP1)+fibroblasts in the entheseal inflammatory microenvironment.ConclusionInflammation-induced aberrant expression of TNC by FSP1+fibroblasts promotes entheseal new bone formation by suppressing ECM adhesion forces and activating Hippo signalling.

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