PXD038008-1

PXD038008 is an original dataset announced via ProteomeXchange.

Title	Modic type 2 changes are fibroinflammatory changes with complement system involvement adjacent to degenerated vertebral endplates
Description	Abstract Background Vertebral endplate signal intensity changes visualized by magnetic resonance imaging termed Modic changes (MC) are highly prevalent in low back pain patients. Interconvertibility between the three MC subtypes (MC1, MC2, MC3) suggests different pathological stages. Histologically, granulation tissue, fibrosis, and bone marrow edema are signs of inflammation in MC1 and MC2. However, different inflammatory infiltrates and amount of fatty marrow suggest distinct inflammatory processes in MC2. Aims The aims of this study were to investigate i) the degree of bony (BEP) and cartilage endplate (CEP) degeneration in MC2, ii) to identify inflammatory MC2 pathomechanisms, and iii) to show that these marrow changes correlate with severity of endplate degeneration. Methods Pairs of axial biopsies (n=58) spanning the entire vertebral body including both CEPs were collected from human cadaveric vertebrae with MC2. From one biopsy, the bone marrow directly adjacent to the CEP was analyzed with mass spectrometry. Differentially expressed proteins (DEPs) between MC2 were identified and bioinformatic enrichment analysis was performed. The other biopsy was processed for paraffin histology and BEP/CEP degenerations were scored. Endplate scores were correlated with DEPs. Results Endplates from MC2 were significantly more degenerated. Proteomic analysis revealed an activated complement system, increased expression of extracellular matrix proteins, angiogenic, and neurogenic factors in MC2 marrow. Endplate scores correlated with upregulated complement and neurogenic proteins. Discussion The inflammatory pathomechanisms in MC2 comprises activation of the complement system. Concurrent inflammation, fibrosis, angiogenesis, and neurogenesis indicate that MC2 is a chronic inflammation. Correlation of endplate damage with complement and neurogenic proteins suggest that complement system activation and neoinnervation may be linked to endplate damage. The endplate-near marrow is the pathomechanistic site, because MC2 occur at locations with more endplate degeneration. Conclusion MC2 are fibroinflammatory changes with complement system involvement which occur adjacent to damaged endplates.
HostingRepository	PRIDE
AnnounceDate	2025-03-21
AnnouncementXML	Submission_2025-03-21_15:03:33.542.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Witold Wolski
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2022-11-07 09:55:12	ID requested
⏵ 1	2025-03-21 15:03:34	announced

Heggli I, Laux CJ, Mengis T, Karol A, Cornaz F, Herger N, Aradi-Vegh B, Widmer J, Burkhard MD, Farshad-Amacker NA, Pfammatter S, Wolski WE, Brunner F, Distler O, Farshad M, Dudli S, Modic type 2 changes are fibroinflammatory changes with complement system involvement adjacent to degenerated vertebral endplates. JOR Spine, 6(1):e1237(2023) [pubmed]

10.1002/jsp2.1237;

submitter keyword: complement system,Label free quantification, inflammation, Human, angiogenesis, Evosep, fibrosis, TimsTof , Modic type 2 changes, neurogenesis, vertebral endplates

Irina Hegli
contact affiliation	Center of Experimental Rheumatology, Department of Rheumatology, University Hospital, University of Zurich, Zurich, Switzerland
contact email	Irina.hegli@uzh.ch
lab head
Witold Wolski
contact affiliation	Functional Genomics Center Zurch
contact email	wew@fgcz.ethz.ch
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD038008
     1. Label: PRIDE project
     2. Name: Modic type 2 changes are fibroinflammatory changes with complement system involvement adjacent to degenerated vertebral endplates