Association of Bone Morphogenetic Proteins with Spinal Fusion in Ankylosing Spondylitis

Hsu, Chung‐Yuan; Chen, Chun-Hsiung; Lin, Yeong‐Jang; Chen, Pei-Chih; Chen, Weisheng; Lu, Chin-Li; Chou, Chen‐Te

doi:10.3899/jrheum.100200

Cited by 64 publications

(51 citation statements)

References 20 publications

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“…The serum level of VEGF then may include both of these components and the predictive effect of VEGF on radiographic progression may be a manifestation of the first or the second, or the sum total of both phenomena. In our patients, the VEGF level did not correlate with BMP-2, which participates in the regulation of bone proliferation, and in patients with AS its level correlated with the spinal score (11). However, the predictive influence on radiographic progression has not been determined in this protein.…”

Section: Discussionmentioning

confidence: 78%

“…Another aim is to compare the BMP-2 (bone morphogenic protein) levels in patients treated and not treated with TNFα inhibitors and to examine the relationship between VEGF and BMP-2. BMP-2 participates in the regulation of bone proliferation and both its increased serum level in patients suffering from advanced AS and a positive correlation with the degree of radiographic changes were demonstrated (11).…”

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confidence: 99%

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The Vegf and BMP-2 Levels in Patients With Ankylosing Spondylitis and the Relationship to Treatment With Tumour Necrosis Factor Alpha Inhibitors

Tošovský

Bradna

Andrýs

et al. 2014

Acta Med. (Hradec Kralove, Czech Repub.)

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Summary:Introduction: Ankylosing spondylitis (AS) is an inflammatory rheumatic disease characterized by the development of osteoproductive changes in the spine which could possibly result in ankylosis. Treatment with tumour necrosis factor alpha (TNFα) inhibitors has proved to be an important step forward in the treatment of this disease, but for the time being it is not clear whether it favourably influences radiographic progression of the disease. Vascular endothelial growth factor most probably plays a role in the development of osteoproductive changes and recently its predictive influence on radiographic progression has been demonstrated. Bone morphogenic protein 2 (BMP-2) participates in the regulation of bone proliferation and its increased serum level has been demonstrated in patients with advanced AS and correlated with the degree of radiographic changes. Aim: The study aims to evaluate the VEGF and BMP-2 levels in patients with ankylosing spondylitis and how these levels relate to the concurrent treatment with TNFα inhibitors. Methods: Sera were evaluated from patients at the Rheumatologic Clinic of the Hradec Králové Faculty Hospital who fulfilled the modified New York Criteria for AS (n = 55). In these patients, the parameters of the activity of the disease (BASDAI = Bath Ankylosing Spondylitis Disease Activity Index, CRP = C-reactive protein) and the concurrent therapy (TNFα inhibitors, n = 21, vs. non-anti TNFα, n = 34) were recorded. The levels of VEGF and BMP-2 were analyzed using the ELISA method. Results: In patients treated with TNFα inhibitors, a significantly lower VEGF level was found when compared to untreated patients (140.3 (109.4; 262.2) vs. 261 (172.4; 396.6) pg/ml; p = 0.02). No difference was found between BMP-2 levels in both groups (treated vs. untreated patients) (254.8 (2301; 267.3) vs. 261.1 (248.6; 273.5) pg/ml; p = 0.24). A correlation analysis did not reveal any relationship between VEG F and BMP-2 (r = 0.057; p = 0.68). Serum levels of VEGF correlated with serum levels of CRP (r = 0.56; p = 0.00001) and the BASDAI value (r = 0.33; p = 0.015). Conclusion: Significantly lower VEGF levels were found in patients treated with TNFα inhibitors versus the untreated patients. These findings are in harmony with some hitherto published analyses and may give evidence of a favourable effect of TNFα inhibitors on radiographic progression. Neither influence on the BMP-2 level by treatment with TNFα inhibitors nor correlation with VEGF levels was demonstrated.

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Section: Discussionmentioning

confidence: 78%

mentioning

confidence: 99%

The Vegf and BMP-2 Levels in Patients With Ankylosing Spondylitis and the Relationship to Treatment With Tumour Necrosis Factor Alpha Inhibitors

Tošovský

Bradna

Andrýs

et al. 2014

Acta Med. (Hradec Kralove, Czech Repub.)

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“…Three specific BMPs have been studied in human AS. The levels of BMP2, BMP4, and BMP7 increased in AS patients with spinal fusion compared with patients without fusion [44]. However, these changes in BMP2 and BMP7 are not specific to AS, since BMP2 and BMP7 also increased in RA patients [45].…”

Section: Discussionmentioning

confidence: 93%

Bone Morphogenetic Protein 6 Polymorphisms Are Associated with Radiographic Progression in Ankylosing Spondylitis

et al. 2014

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Background and ObjectNearly 25 genetic loci associated with susceptibility to ankylosing spondylitis (AS) have been identified by several large studies. However, there have been limited studies to identify the genes associated with radiographic severity of the disease. Thus we investigated which genes involved in bone formation pathways might be associated with radiographic severity in AS.MethodsA total of 417 Korean AS patients were classified into two groups based on the radiographic severity as defined by the modified Stoke’ Ankylosing Spondylitis Spinal Score (mSASSS) system. Severe AS was defined by the presence of syndesmophytes and/or fusion in the lumbar or cervical spine (n = 195). Mild AS was defined by the absence of any syndesmophyte or fusion (n = 170). A total of 251 single nucleotide polymorphisms (SNPs) within 52 genes related to bone formation were selected and genotyped. Odds ratios (OR) and 95% confidence interval (95% CI) were analysed by multivariate logistic regression controlling for age at onset of symptoms, sex, disease duration, and smoking status as covariates.ResultsWe identified new loci of bone morphogenetic protein 6 (BMP6) associated with radiographic severity in patients with AS that passed false discovery rate threshold. Two SNPs in BMP6 were significantly associated with radiologic severity [rs270378 (OR 1.97, p = 6.74×10−4) and rs1235192 [OR 1.92, p = 1.17×10−3]) adjusted by covariates.ConclusionThis is the first study to demonstrate that BMP6 is associated with radiographic severity in AS, supporting the role wingless-type like/BMP pathway on radiographic progression in AS.

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“…Among the BMPs, BMP-2 has been demonstrated to have the most marked osteogenic capacity (5,6). Notably, serum levels of BMP-2 in AS patients with spinal fusion is higher than healthy controls or AS patients without spinal fusion (7). In in vitro studies, BMP-2 has been shown to induce osteogenic differentiation of fibroblasts (5,6).…”

Section: Introductionmentioning

confidence: 99%

Bushen-Qiangdu-Zhilv decoction inhibits osteogenic differentiation of rat fibroblasts by regulating connexin 43

Zhou

Huang

Lin

et al. 2016

Experimental and Therapeutic Medicine

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Abstract. Bushen-Qiangdu-Zhilv (BQZ) decoction is a traditional Chinese medicinal compound widely used for treating ankylosing spondylitis (AS). However, the mechanisms underlying effects of BQZ remain largely unknown. Osteoblast differentiation of fibroblasts plays an important role in heterotopic ossification (HO) of AS, and connexin 43 (Cx43) is crucially involved in the osteoblast differentiation of fibroblasts. The aim of the present study was to evaluate the effects of BQZ on the osteogenic differentiation of fibroblasts by regulating Cx43. Rat fibroblasts were treated with freeze-dried powder of BQZ, in the presence or absence of recombinant human bone morphogenetic protein-2 (rhBMP-2). MTS assays were performed to examine the inhibitory effects of BQZ on fibroblast proliferation. Western blot assays were conducted to detect the protein expression of core-binding factor alpha 1 (Cbfα1), Cx43 and phosphorylated Cx43 (pCx43). BQZ appeared to inhibit fibroblast proliferation in a dose-dependent manner. Furthermore, the expression of Cbfα1 and Cx43/pCx43 was significantly suppressed by BQZ, with or without rhBMP-2 stimulation. Therefore, the present results indicate that BQZ may exert an anti-AS effect by suppressing the osteogenic differentiation of fibroblasts via Cx43 regulation.

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Association of Bone Morphogenetic Proteins with Spinal Fusion in Ankylosing Spondylitis

Abstract: Rising levels of BMP in AS patients with spinal fusion and the positive correlation between BMP and spinal radiograph scores indicate that BMP may play a role in the process of spinal ankylosis. Serum levels of BMP may reflect radiographic progression of the spine and hip joints.

Cited by 64 publications

References 20 publications

The Vegf and BMP-2 Levels in Patients With Ankylosing Spondylitis and the Relationship to Treatment With Tumour Necrosis Factor Alpha Inhibitors

The Vegf and BMP-2 Levels in Patients With Ankylosing Spondylitis and the Relationship to Treatment With Tumour Necrosis Factor Alpha Inhibitors

Bone Morphogenetic Protein 6 Polymorphisms Are Associated with Radiographic Progression in Ankylosing Spondylitis

Bushen-Qiangdu-Zhilv decoction inhibits osteogenic differentiation of rat fibroblasts by regulating connexin 43

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