Mutual role of PGRN/TNF-α on osteopenia developing in obesity's inflammation state.
OBJECTIVE
The aim of the study was to investigate the concentration of PGRN and other inflammatory cytokines TNF-α, IL-1β, IL-4, IL-6, IL-10, IL-13 and IL-17 in osteopenic and non-osteopenic obese subjects. Bone mineral density in subjects with different PGRN levels were compared to the appraisal of our hypothesis.


METHODS
A total of 171 obese participants (BMI ≥30) were included in the study. Analysis of body composition was performed with use of Body Composition Analyzer. All blood samples were collected between 8:00 and 10:00 a.m. following an overnight fasting. The circulating levels of TNF-α, PGRN, IL-1β, IL-4, IL-6, IL-10, IL-13, IL-17, PTH, 25-Hydroxy Vitamin D and crosslaps were measured with the EIA method. BMD was measured by use of dual energy X-ray absorptiometery (DXA) at lumbar spine (vertebrae L2-L4) and hip level. Participants were categorized into osteopenic and healthy group according to the World Health Organization (WHO) criteria. Of 171 participants, 51 (29.82 %) were osteopenic and 120 (70.17%) were healthy.


RESULTS
We found significantly higher concentrations of crosslaps, IL-17, IL-6, TNFα and IL-4 and lower concentrations of IL-13, IL-10, PGRN and free fat mass in osteopenic group. With raising the PGRN level, the concentrations of IL-13, IL-10 and 25-(OH) vitamin D were increased and the concentration of TNFα and IL-17 were decreased. Our results demonstrated that the density of bone at both sites of lumbar spine (L2-L4) and hip region was highest in 4th quartile and lowest in first quartile of categorized PGRN concentration. The bone status was gradually improved with raising the PGRN level in parallel at lumbar spine (L2-L4) and hip regions.


CONCLUSIONS
Based on the pathway of effect of TNFα on bone metabolism, it appears that PGRN acts on the bone with mechanisms involving TNFR signaling, disturbance and TNFα performance, similar to the results that have been found in animal model study.
Tehran University of Medical Sciences, Tehran, Iran. ahosseinnezhad@sina.tums.ac.ir
A
A
Hossein-Nezhad
K
K
Mirzaei
H
H
Ansar
G
G
Khooshechin
Z
Z
Ahmadivand
S A
SA
Keshavarz
D015652:25-Hydroxyvitamin D 2 / Q000097:blood; D000328:Adult; D015415:Biomarkers / Q000097:blood; D001823:Body Composition; D015519:Bone Density; D001851:Bone Diseases, Metabolic / Q000097:blood* / Q000503:physiopathology; D003094:Collagen / Q000097:blood; D005260:Female; D006615:Hip / Q000503:physiopathology; D006801:Humans; D007249:Inflammation / Q000097:blood* / Q000209:etiology / Q000503:physiopathology; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood*; D007378:Interleukins / Q000097:blood; D007492:Iran / Q000208:ethnology; D008161:Lumbosacral Region; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood* / Q000150:complications / Q000503:physiopathology; D010281:Parathyroid Hormone / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D000077153:Progranulins; D011498:Protein Precursors / Q000097:blood*; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood; D013131:Spine / Q000503:physiopathology; D014409:Tumor Necrosis Factor-alpha / Q000097:blood*; D055815:Young Adult
D015415:Biomarkers; C492314:GRN protein, human; D036341:Intercellular Signaling Peptides and Proteins; D007378:Interleukins; D010281:Parathyroid Hormone; D010446:Peptide Fragments; D000077153:Progranulins; D011498:Protein Precursors; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; C110762:glutamyl-lysyl-alanyl-histidyl-aspartyl-glycyl-glycyl-arginine; D015652:25-Hydroxyvitamin D 2; D003094:Collagen