Insight on Bone Morphogenetic Protein 7 in Ankylosing Spondylitis and its association with disease activity and radiographic damage

Abstract

IntroductionFusion of joints as well as intervertebral spaces by the formation of bony spurs appearing as syndesmophytes and osteophytes are the hallmark of spondyloarthropathies which accounts for disability. The aim of this study was to assess the serum level of bone morphogenetic protein (BMP)-7 in ankylosing spondylitis and its relationship with disease activity and the radiographic damage.MethodsThis longitudinal case control study was conducted in Ain Shams University Hospitals (Egypt). A total of 55 subjects were included in two case groups and one control group. Group I included 20 patients with Ankylosing Spondylitis (AS) assessed at baseline (defined as Ia and after 18 months defined as Ib). Group II included 20 patients with Rheumatoid Arthritis (RA) and Group III included 15 healthy subjects as controls. Patients with other forms of seronegative spondyloarthropathies, bone forming diseases were excluded from the study. The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and the Bath Ankylosing Spondylitis Metrology Index (BASMI) were used to assess disease activity in AS patients. RA disease activity was assessed using the disease activity score 28 (DAS28). Radiographic changes were assessed using the Bath AS Radiographic Index (BASRI) in AS and Larsen scores in RA. Laboratory investigations included: Complete blood picture (CBC), Erythrocyte sedimentation rate (ESR), quantitative CRP, serum calcium, phosphorus and alkaline phosphatase. Determination of serum bone morphogenetic protein-7 level (BMP-7) was done using enzyme linked immunosorbent assay (ELISA). Sample collections, clinical and radiological assessments were performed at baseline for all groups and after a mean follow-up of 18 months for Group I. Data were analyzed by SPSS 17, using t-test, Kruskal-Wallis, Mann-Whitney, Fischer exact test, Chi square, and Pearson Product-Moment Correlation Coefficient.ResultsThere were statistically significant differences between the 3 groups as regard baseline BMP-7 levels; the mean BMP-7 level of AS patients was significantly higher than that of RA patients and controls and significantly higher in the RA group than that of controls. BMP-7 levels were not associated with any of the clinical or drug related variables either in AS or RA. In AS BMP-7 levels showed significant increase after follow up and significant positive correlation with serum alkaline phosphatase (both at baseline and after follow up) and BASDAI score (after follow up) respectively. Despite the parallel increase of BMP7 and BASRI score during the follow-up period no statistically significant correlation was detected. There were no significant correlations between BMP7 level and patient’s age or any disease related characteristics in the RA group.ConclusionA significant progressive increase in serum BMP-7 was noted in AS patients that correlated with serum markers of bone formation. Such a biomarker measurement may not only act as a surrogate marker for the disease but has the potential to contribute to the pathogenesis of A...

Association study of copy number variation in BMP8A gene with the risk of ankylosing spondylitis in Iranian population

“…In some studies, the difference in their results was reported for the differences in the disease stages and the severity of bone injuries. 40,46 In conclusion, the BMP8A CNVs seem to play no role in susceptibility to AS in Iranian population. Although it might not be regulated by CNVs, BMP8a may have a role in the pathogenesis of AS.…”

“…It seems, based on the evidence, that our results of gene expression can be dependent on the induction time, the condition, and the phase or stage of the disease. In some studies, the difference in their results was reported for the differences in the disease stages and the severity of bone injuries …”

“…Studies reported a high level of BMP2 and 7 in association with serum markers of bone formation in patients with AS. [40][41][42] It can be said that the signaling pathway of these proteins is complex, depending on time and cell contents. Some findings imply to the crosstalk between BMP signaling and other pathways, such as Wnt and Hedgehog, and its positive or negative effects.…”

A2A adenosine receptor agonist reduced MMP8 expression in healthy M2-like macrophages but not in macrophages from ankylosing spondylitis patients

“…Of these, BMP-2 is an active and important member which can independently or synergistically with other signaling pathways like the Wnt/β-catenin pathway, enhance osteoblast differentiation and bone formation [ 10 , 11 ]. Data regarding the level of these proteins in AS patients are incompatible; however, most of them show higher levels of these proteins in patients compared to healthy controls [ 12 , 13 ].…”

A2A adenosine receptor agonist reduced MMP8 expression in healthy M2-like macrophages but not in macrophages from ankylosing spondylitis patients

“…Of these, BMP-2 is an active and important member which can independently or synergistically with other signaling pathways like the Wnt/β-catenin pathway, enhance osteoblast differentiation and bone formation [10,9]. Data regarding the level of these proteins in AS patients are incompatible; however, most of them show higher levels of these proteins in patients compared to healthy controls [11,12].…”