Tissue and extracellular matrix remodeling of the subchondral bone during osteoarthritis of knee joints as revealed by spatial mass spectrometry imaging
Year: 2026
Type: article
Study design: Observational Study
Abstract: Osteoarthritis (OA) is a degenerative skeletal condition marked by the loss of articular cartilage and changes to subchondral bone homeostasis. Treatments for OA beyond full joint replacement are lacking primarily due to gaps in molecular knowledge of the biological drivers of disease. Mass Spectrometry Imaging (MSI) enables molecular spatial mapping of the proteomic landscape of tissues. Histologic sections of human tibial plateaus from knees of human OA patients and cadaveric controls were treated with collagenase III to target extracellular matrix (ECM) proteins prior to MS Imaging of bone and cartilage proteins. Spatial MS imaging of the knee identified distinct areas of joint damage to the subchondral bone underneath areas of lost cartilage. This damaged bone signature extended underneath remaining cartilage in OA joints, indicating subchondral bone remodeling could occur before full thickness cartilage loss in OA. Specific ECM peptide markers from OA-affected medial tibial plateaus were compared to their healthier lateral halves from the same patient, as well as to healthy, age-matched cadaveric knees. Overall, 31 peptide candidates from ECM proteins, including Collagen alpha-1(I), Collagen alpha-1(III), and surprisingly, Collagen alpha-1(VI) and Collagen alpha-3(VI), exhibited significantly elevated abundance in diseased tissues. Additionally, highly specific hydroxyproline-containing collagen peptides, mainly from collagen type I, dominated OA subchondral bone directly under regions of lost cartilage but not areas where cartilage remained intact. A separate analysis of synovial fluid from a second cohort of OA patients found similar regulation of collagens and ECM proteins via LC-MS/MS demonstrating that markers of subchondral bone remodeling discovered by MALDI-MS may be detectable as biomarkers in biofluid samples. The identification of specific protein markers for subchondral bone remodeling in OA advances our molecular understanding of disease progression in OA and provides potential new biomarkers for OA detection and disease grading.
Source: Bone Research
Language: English
Subfield: Rheumatology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,405
Funders: U.S. Department of Defense, National Institutes of Health, National Institute on Aging, NIH Office of the Director, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institute of Dental and Craniofacial Research, Division of Cancer Epidemiology and Genetics, National Cancer Institute
Awards: G129399213, G2091789702, G2141279964, G2291616305, G2414471534, G2441775484, G2800152382, G2969411523, G3259649635, Spatial Proteomics of osteoarthritis in bones to uncover disease progression, G3694428558, Bruker scimaX™ Magnetic Resonance Mass Spectrometer, G4312914480, G444656065, G4615953562, IDENTIFICATION OF NOVEL OSTEOCYTE-REGULATORY THERAPIES TO PREVENT AND TREAT PTOA IN WARFIGHTERS, Enzymatic Tools for 2D Tissue Localized and Deeper Proteomic Sequencing of Cancer Stromal Proteins, G6998434892, G7015462466, G9000018839, G9000146486, G9000152989, G9000184454, G9000213115, Cellular senescence and cell fate/interactions as drivers of Alzheimer's and age-related dementias, Senescent cell mapping, identification and validation for human somatic and reproductive tissues, timsTOF fleX MALDI-2 for Spatial Molecular Imaging, Training in Basic Research on Aging and Age-Related Disease
OpenAlex ID: W7125638510