Evidence map›Paper›PMID 41587965›Full record

ArticleBone research2026

Tissue and extracellular matrix remodeling of the subchondral bone during osteoarthritis of knee joints as revealed by spatial mass spectrometry imaging.

Charles A Schurman, Joanna Bons, Jonathon J Woo, Cristal Yee, Qi Liu, Nannan Tao, Tamara Alliston, Peggi Angel, Birgit Schilling

Abstract read
In one paragraph

Article in Bone research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

7 citing papers in PubMed.

  1. Article
  2. Article
  3. Alzheimer's Disease Risk Factor APOE4 Exerts Dimorphic Effects on Female Bone.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  4. Article
  5. Article
  6. Article
  7. Osteoarthritis as a systemic disease.Nature reviews. Rheumatology · 2026
    Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors.

Charles A SchurmanBuck Institute for Research on Aging, Novato, CA, USA.
Joanna BonsBuck Institute for Research on Aging, Novato, CA, USA.ORCID 0000-0002-1110-4193
Jonathon J WooDepartment of Orthopaedic Surgery, University of California San Francisco, San Francisco, CA, USA.ORCID 0000-0002-8996-6754
Cristal YeeDepartment of Orthopaedic Surgery, University of California San Francisco, San Francisco, CA, USA.
Qi LiuBuck Institute for Research on Aging, Novato, CA, USA.
Nannan TaoBruker Daltonics Inc, San Jose, CA, USA.
Tamara AllistonDepartment of Orthopaedic Surgery, University of California San Francisco, San Francisco, CA, USA.
Peggi AngelDepartment of Pharmacology & Immunology, Medical University of South Carolina, Charleston, SC, USA.
Birgit SchillingBuck Institute for Research on Aging, Novato, CA, USA. bschilling@buckinstitute.org.ORCID 0000-0001-9907-2749

Funding

Single cell analysis coreP01AG066591 · NIA · BUCK INSTITUTE FOR RESEARCH ON AGING · PI MELOV, SIMON · 2021 to 2025
$15.5M
Training in Basic Research on Aging and Age-Related DiseaseT32AG000266 · NIA · UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB · PI Lisa M Ellerby · 1998 to 2026
$13.8M
Senescent cell mapping, identification and validation for human somatic and reproductive tissuesU54AG075932 · NIA · BUCK INSTITUTE FOR RESEARCH ON AGING · PI Simon Melov, Birgit Schilling · 2021 to 2026
$12.5M
The mechanistic control of bone quality and joint crosstalk by osteocytesR01DE019284 · NIDCR · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI HERNANDEZ, CHRISTOPHER JOHN · 2009 to 2024
$7.6M
Quantitative Proteomics to Develop Robust Senescence-Related Biomarkers for AgingU01AG060906 · NIA · BUCK INSTITUTE FOR RESEARCH ON AGING · PI SCHILLING, BIRGIT · 2018 to 2022
$4.0M
UCSF Core Center for Musculoskeletal Biology and MedicineP30AR066262 · NIAMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MAJUMDAR, SHARMILA · 2014 to 2018
$3.0M
timsTOF fleX MALDI-2 for Spatial Molecular ImagingS10OD038264 · OD · BUCK INSTITUTE FOR RESEARCH ON AGING · PI SCHILLING, BIRGIT · 2025 to 2025
$1.8M
Bruker scimaX™ Magnetic Resonance Mass SpectrometerS10OD030212 · OD · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI ANGEL, PEGGI M · 2021 to 2021
$1.7M
Enzymatic Tools for 2D Tissue Localized and Deeper Proteomic Sequencing of Cancer Stromal ProteinsR21CA240148 · NCI · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI ANGEL, PEGGI M · 2019 to 2020
$480k
Spatial Proteomics of osteoarthritis in bones to uncover disease progressionR21AR084303 · NIAMS · BUCK INSTITUTE FOR RESEARCH ON AGING · PI ALLISTON, TAMARA N, ANGEL, PEGGI M · 2024 to 2024
$457k
Osteocyte-dependent mechanisms of bone cartilage crosstalk in osteoarthritisR21AR083065 · NIAMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI AKBAS KAYA, AYSE SERRA · 2023 to 2023
$409k
NCI NIH HHS R21 CA240148NIAMS NIH HHS P30 AR066262NIAMS NIH HHS R21 AR083065NIAMS NIH HHS R21 AR084303NIA NIH HHS P01 AG066591NIA NIH HHS T32 AG000266NIA NIH HHS U01 AG060906NIA NIH HHS U54 AG075932NIDCR NIH HHS R01 DE019284NIH HHS S10 OD030212NIH HHS S10 OD038264ODCDC CDC HHS S10 OD030212ODCDC CDC HHS S10 OD038264U.S. Department of Defense (United States Department of Defense) DOD HT94252310875U.S. Department of Defense (United States Department of Defense) DOD PRORP OR130191U.S. Department of Defense (United States Department of Defense) DOD PRORP W81XWH1810155
6 · The paper itself

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.

Indexed as

Bone and BonesBone RemodelingExtracellular MatrixKnee JointMass SpectrometryOsteoarthritis, KneeAgedBiomarkersExtracellular Matrix ProteinsFemaleHumansMaleMiddle AgedBiomarkersExtracellular Matrix Proteins

Identifiers

PMID41587965
PMCPMC12835079

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.