Increased serum levels of MIC1/GDF15 correlated with bone erosion in spondyloarthritis

Abstract

Introduction:To assess the association between growth differentiation factor-15 (GDF15) and radiographic features including bone marrow edema and bone erosion in Spondyloarthritis (SpA).Methods:Patients with SpA (n = 120) receiving treatment in the Guangdong General Hospital, China, between August 2012 and December 2016 were retrospectively included. Serum of patients and healthy controls (n = 30) were collected and GDF15 levels were measured using ELISA. Inflammation was assessed by C-reactive protein (CRP), and magnetic resonance imaging (MRI) of the sacroiliac joint using Spondyloarthritis Research Consortium of Canada score and a method of dichotomy to assess fat metaplasia, bone erosion, and ankylosis. Radiographs of the pelvis were scored using the modified New York (mNY) score.Results:Serum GDF15 levels were higher in SpA patients compared to controls (503.52 ± 222.92 vs. 190.86 ± 104.18 pg/mL, P < .0001). Patients who suffered from bone erosion on MRI had higher levels of GDF15 (525.72 [186.33, 801.62]vs. 428.06 [255.15, 670.98] pg/mL, P = .0375). There was a positive correlation between serum GDF15 and CRP (r = 0.5442, P < .0001). Moreover, GDF15 levels were related to CRP levels (r = 0.5658, P < .0001) in those X-ray scores were III, according to 1984mNY criteria. Receiver operating characteristic (ROC) analysis showed that GDF15 levels above 501.98pg/mL could predict presence of bone erosion on MRI.Conclusion:The present study suggested that serum GDF15 levels are higher in SpA patients than in healthy controls. The GDF15 level was correlated with CRP and may be a surrogate biomarker in bone erosion.

Pathophysiological pathways related to high plasma growth differentiation factor 15 concentrations in patients with heart failure

“…Pathway analysis found upregulation in bone and tissue remodelling, which is in line with previous literature, as GDF‐15 has been related to osteoclast differentiation, being attenuated by bone hypoxia 23,50 . Key players in these pathways were osteopontin, IL‐6 and TNFRSF11A.…”

“…GDF‐15 has been found to suppress osteopontin secretions in fibrotic liver disease, likely acting as a liver protective protein, in line with our findings, as high GDF‐15 was significantly linked to hepatomegaly 54,55 . The bone regulatory effects of GDF‐15 have been linked to bone metastasis in cancer and spondylarthritis, however its exact role in HF remains unclear 24,25,50 …”

“…54,55 The bone regulatory effects of GDF-15 have been linked to bone metastasis in cancer and spondylarthritis, however its exact role in HF remains unclear. 24,25,50 Strongest GDF-15 associated biomarkers WISP-1 is an extracellular matrix protein expressed by fibroblasts in the heart, lungs, kidneys, spleen, pancreas and brain among others. 56 Further, WISP-1 is highly expressed in visceral adipose tissue where it may reflect adipose tissue inflammation and insulin resistance, and is elevated in obesity and in reaction to oxLDL.…”

“…Pathway analysis found upregulation in bone and tissue remodelling, which is in line with previous literature, as GDF-15 has been related to osteoclast differentiation, being attenuated by bone hypoxia. 23,50 Key players in these pathways were osteopontin, IL-6 and TNFRSF11A. Osteopontin inhibits myeloid cell recruitment and metalloproteinase expression, regulates osteoclast differentiation, and has a pleiotropic effect on vascular remodelling.…”

Epicardial adipose tissue thickness and growth differentiation factor 15 in axial spondyloarthritis

“…[13][14][15] Some studies that found GDF-15 levels to be higher in RA and axSpA than in healthy people. 12,16 However, data on this subject are insufficient.…”