Serum Functional Dickkopf-1 Levels Are Inversely Correlated with Radiographic Severity of Ankylosing Spondylitis

Zou, Yong; Lu, Lu; Shengfa, Li; Ye, Yongliang; Ruguo, Shang; Li, Yikai

doi:10.7754/clin.lab.2014.131119

Cited by 31 publications

(25 citation statements)

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“…Inconsistent data regarding expression levels of DKK-1 in AS patients have been reported, with some studies showing decreased DKK-1 expression in AS patients compared to healthy controls or RA patients, while other studies have refuted this [114, 78, 115-117]. However, DKK-1 serum levels do not necessarily correlate with functional activity of the DKK-1 protein.…”

Section: Spondyloarthritismentioning

confidence: 99%

Mediators of inflammation and bone remodeling in rheumatic disease

Shaw

Gravallese

2016

Seminars in Cell & Developmental Biology

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Remodeling of bone is a continuous process that occurs throughout life. Under normal physiologic conditions, bone-resorbing osteoclasts and bone-forming osteoblasts are tightly coupled and regulated to ensure the proper balance, such that there is no net change in bone mass. However, inflammation perturbs normal bone homeostasis. The impact of inflammation on bone is dependent upon the anatomic site affected, cell types, factors and cytokines present in the local microenvironment, and local mechanical forces. Cytokines are central to the pathogenesis of inflammation-induced bone loss and contribute to the uncoupling of osteoclast-mediated bone resorption and osteoblast-mediated bone formation, thereby disrupting normal remodeling. In this review, we will discuss the effects of cytokines on bone in two settings, rheumatoid arthritis (RA) and spondyloarthritis (SpA), a disease category that includes ankylosing spondylitis (AS), psoriatic arthritis (PsA), reactive arthritis, inflammatory bowel disease, and juvenile onset spondyloarthropathy. The outcome for bone in these disease settings is quite different, and an understanding of the pathogenic mechanisms leading to the net impact on bone has been essential in developing new therapeutic approaches to bone health in these diseases.

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Section: Spondyloarthritismentioning

confidence: 99%

Mediators of inflammation and bone remodeling in rheumatic disease

Shaw

Gravallese

2016

Seminars in Cell & Developmental Biology

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“…In general, Dkk1 levels have been described as being lower in most [50, 67–69] but not all studies [46, 51]. Furthermore, AS patients with no syndesmophyte formation have been shown to have significantly higher functional Dkk1 levels, suggesting that blunted Wnt signaling suppresses new bone formation and consequently syndesmophyte growth and spinal ankylosis [66, 67], although they were not affected by 3-month anti-TNF-α therapy [68]. In yet another study [50], patients with AS had significantly higher serum levels of Wnt-3a compared with the controls.…”

Section: Markers Of Radiographic Severity and Progression (Table 3)mentioning

confidence: 99%

Biomarkers for diagnosis, monitoring of progression, and treatment responses in ankylosing spondylitis and axial spondyloarthritis

Reveille

2015

Clin Rheumatol

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With the growing awareness of the impact of chronic back pain and axial spondyloarthritis and recent breakthroughs in genetics and the development of novel treatments which may impact best on early disease, the need for markers that can facilitate early diagnosis and profiling those individuals at the highest risk for a bad outcome has never been greater. The genetic basis of ankylosing spondylitis has been considerably advanced, and HLA-B27 testing has a role in the diagnosis. Knowledge is still incomplete of the rest of the genetic contribution to disease susceptibility, and it is likely premature to use extensive genetic testing (other than HLA-B27) for diagnosis. Serum and plasma biomarkers have been examined extensively in assessing disease activity, treatment response, and as predictors or radiographic severity. For assessing disease activity, other than C-reactive protein and erythrocyte sedimentation rate, the most work has been in examining cytokines (particularly interleukin 17 and 23), matrix metalloproteinase (MMP) markers (particularly MMP3). For assessing those at the highest risk for radiographic progression, biomarkers of bony metabolism, cartilage and connective tissue degradation products, and adipokines have been most extensively assessed. The problem is that no individual biomarkers has been reproducibly shown to assess disease activity or predict outcome, and this area still remains an unmet need, of relevance to industry stakeholders, to regulatory bodies, to the healthcare system, to academic investigators, and finally to patients and providers.

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“…Dickkopf-1 (DKK-1) is a natural inhibitor of Wnt signaling that can induce OPG production and that is devoted to osteoblastogenesis. In contrast to increased DKK-1 in RA, serum DKK-1 in AS has been reported to be decreased and to be inversely correlated with AS disease severity (Yucong et al, 2014). Blockade of DKK-1 in mice induces ankylosis of sacroiliac joints (Uderhardt et al, 2010), indicating that manipulating Wnt signaling may be a promising therapeutic strategy to prevent osteophyte formation at the inflammation site (Schett et al, 2008).…”

Section: Spa (Spondyloarthropathy)mentioning

confidence: 99%

Osteoimmunology: memorandum for rheumatologists

Huang

Zhang

2016

Sci. China Life Sci.

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Rapid progress has been made in exploring the connections between the skeletal system and the immune system over the past decade. Bone tissue forms developmental niches for hematopoietic stem cells, and activated immune cells are involved in bone metabolism regulation and are potent mediators of osteoporosis and bone erosion under pathological conditions. The interdisciplinary field of osteoimmunology has emerged to pool the knowledge of the interdependence of these two systems, including the shared ligands and receptors, their crosstalk and interaction, and common intracellular signaling pathways with bidirectional influence. The receptor activator of nuclear factor-kappa B (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) triad is the key vinculum, with multifaceted potency, being not only essential for osteoclastogenesis but also critical for lymph node organogenesis and lymphopoiesis as well as for immune regulation. In this review, we summarize the progress in this area, focusing on those aspects of interest concerning rheumatic diseases. osteoimmunology, bone remodeling, osteoclastogenesis, immune cells, RANKLCitation:

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Serum Functional Dickkopf-1 Levels Are Inversely Correlated with Radiographic Severity of Ankylosing Spondylitis

Cited by 31 publications

References 0 publications

Mediators of inflammation and bone remodeling in rheumatic disease

Mediators of inflammation and bone remodeling in rheumatic disease

Biomarkers for diagnosis, monitoring of progression, and treatment responses in ankylosing spondylitis and axial spondyloarthritis

Osteoimmunology: memorandum for rheumatologists

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