MassIVE MSV000094448

Partial Public PXD051135

Mass Spectrometry Imaging of the Extracellular Matrix of the Subchondral Bone in Osteoarthritis Provides Evidence of Tissue Remodeling on the Protein Level that May Precede Cartilage Loss

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Description

Osteoarthritis (OA) of the knee is a degenerative condition of the skeletal extracellular matrix (ECM) marked by the loss of articular cartilage and subchondral bone homeostasis that preferentially occurs in the medial side of the joint. Treatments for OA beyond full joint replacement are lacking primarily due to gaps in molecular knowledge of the biological drivers for disease progression. MALDI-Mass Spectrometry Imaging (MSI) allows molecular spatial mapping that is used to investigate the proteomic landscape of OA providing molecular details on the progression of joint degeneration. Entire histologic sections of human tibial plateaus from OA patients and cadaveric controls were treated with collagenase III to target ECM proteins prior to imaging using a timsTOF flex mass spectrometer (Bruker) for the first reported study of MALDI-MSI on bone protein. Data from healthy cadaveric joints and both lateral and medial sides of OA joints were automatically segmented identifying distinct areas of joint damage. Candidate ECM markers comparing either OA to cadaveric tissues or OA medial to OA lateral tissues resulted in 44 candidate peptides that emphasize the significant spatial difference between OA and healthy bone (AUROC >0.85). 31 of 44 peptide markers, resulting from ECM proteins such as COL1A1, COL3A1, and novel detection of COL6A1 and COL6A3 in bone, with significantly elevated abundance in our full OA cohort, indicate disease progression. Spatial maps of these markers revealed distinct tissue damage and disease pathologies in the subchondral bone that are related to protein structural changes in the ECM, changes that may precede overlying cartilage loss in OA. [doi:10.25345/C5HQ3S91K] [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: Osteoarthritis ; MALDI Imaging ; Extracellular Matrix ; Cartilage ; Subchondral Bone

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Principal Investigators:
(in alphabetical order) 		Birgit Schilling, Buck Institute, USA
Submitting User: cschurman
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