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Biomarkers of inflammation and innate immunity in atrophic nonunion fracture.
- Source :
-
Journal of translational medicine [J Transl Med] 2016 Sep 06; Vol. 14, pp. 258. Date of Electronic Publication: 2016 Sep 06. - Publication Year :
- 2016
-
Abstract
- Background: Nonunion is a failure of healing following a bone fracture. Its physiopathology remains partially unclear and the discovery of new mediators could promote the understanding of bone healing.<br />Methods: Thirty-three atrophic nonunion (NU) patients that failed to demonstrate any radiographic improvement for 6 consecutive months were recruited for providing serum samples. Thirty-five healthy volunteers (HV) served as the control group. Proteomics studies were performed using SELDI-TOF-MS and 2D-DIGE approaches, associated or not with Proteominer® preprocessing, to highlight biomarkers specific to atrophic nonunion pathology. Peak intensities were analyzed by two statistical approaches, a nonparametric Mann-Whitney U tests (univariate approach) and a machine-learning algorithm called extra-trees (multivariate approach). Validation of highlighted biomarkers was performed by alternative approaches such as microfluidic LC-MS/MS, nephelometry, western blotting or ELISA assays.<br />Results: From the 35 HV and 33 NU crude serum samples and Proteominer® eluates, 136 spectra were collected by SELDI-TOF-MS using CM10 and IMAC-Cu(2+) ProteinChip arrays, and 665 peaks were integrated for extra-trees multivariate analysis. Accordingly, seven biomarkers and several variants were identified as potential NU biomarkers. Their levels of expression were found to be down- or up-regulated in serum of HV vs NU. These biomarkers are inter-α-trypsin inhibitor H4, hepcidin, S100A8, S100A9, glycated hemoglobin β subunit, PACAP related peptide, complement C3 α-chain. 2D-DIGE experiment allowed to detect 14 biomarkers as being down- or up-regulated in serum of HV vs NU including a cleaved fragment of apolipoprotein A-IV, apolipoprotein E, complement C3 and C6. Several biomarkers such as hepcidin, complement C6, S100A9, apolipoprotein E, complement C3 and C4 were confirmed by an alternative approach as being up-regulated in serum of NU patients compared to HV controls.<br />Conclusion: Two proteomics approaches were used to identify new biomarkers up- or down-regulated in the nonunion pathology, which are involved in bone turn-over, inflammation, innate immunity, glycation and lipid metabolisms. High expression of hepcidin or S100A8/S100A9 by myeloid cells and the presence of advanced glycation end products and complement factors could be the result of a longstanding inflammatory process. Blocking macrophage activation and/or TLR4 receptor could accelerate healing of fractured bone in at-risk patients.
- Subjects :
- Adolescent
Adult
Aged
Amino Acid Sequence
Case-Control Studies
Demography
Female
Hepcidins metabolism
Humans
Male
Middle Aged
Proteomics
Reproducibility of Results
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
Two-Dimensional Difference Gel Electrophoresis
Young Adult
Biomarkers metabolism
Fractures, Ununited immunology
Fractures, Ununited pathology
Immunity, Innate
Inflammation metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1479-5876
- Volume :
- 14
- Database :
- MEDLINE
- Journal :
- Journal of translational medicine
- Publication Type :
- Academic Journal
- Accession number :
- 27599571
- Full Text :
- https://doi.org/10.1186/s12967-016-1019-1