Cell and transcriptomic diversity of infrapatellar fat pad during knee osteoarthritis.

Arthritis Fibroblasts Osteoarthritis Osteoarthritis, Knee Risk Factors

Journal

Annals of the rheumatic diseases
ISSN: 1468-2060
Titre abrégé: Ann Rheum Dis
Pays: England
ID NLM: 0372355

Informations de publication

Date de publication:
07 Oct 2024
Historique:
received: 05 04 2024
accepted: 19 09 2024
medline: 8 10 2024
pubmed: 8 10 2024
entrez: 7 10 2024
Statut: aheadofprint

Résumé

In this study, we employ a multiomic approach to identify major cell types and subsets, and their transcriptomic profiles within the infrapatellar fat pad (IFP), and to determine differences in the IFP based on knee osteoarthritis (KOA), sex and obesity status. Single-nucleus RNA sequencing of 82 924 nuclei from 21 IFPs (n=6 healthy control and n=15 KOA donors), spatial transcriptomics and bioinformatic analyses were used to identify contributions of the IFP to KOA. We mapped cell subclusters from other white adipose tissues using publicly available literature. The diversity of fibroblasts within the IFP was investigated by bioinformatic analyses, comparing by KOA, sex and obesity status. Metabolomics was used to further explore differences in fibroblasts by obesity status. We identified multiple subclusters of fibroblasts, macrophages, adipocytes and endothelial cells with unique transcriptomic profiles. Using spatial transcriptomics, we resolved distributions of cell types and their transcriptomic profiles and computationally identified putative cell-cell communication networks. Furthermore, we identified transcriptomic differences in fibroblasts from KOA versus healthy control donor IFPs, female versus male KOA-IFPs and obese versus normal body mass index (BMI) KOA-IFPs. Finally, using metabolomics, we defined differences in metabolite levels in supernatants of naïve, profibrotic stimuli-treated and proinflammatory stimuli-treated fibroblasts from obese compared to normal BMI KOA-IFPs. Overall, by employing a multiomic approach, this study provides the first comprehensive map of the cellular and transcriptomic diversity of human IFP and identifies IFP fibroblasts as key cells contributing to transcriptomic and metabolic differences related to KOA disease, sex or obesity.

Identifiants

DOI: 10.1136/ard-2024-225928 PMID: 39375009
pubmed: 39375009
pii: ard-2024-225928
doi: 10.1136/ard-2024-225928
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ on behalf of EULAR.

Déclaration de conflit d'intérêts

Competing interests: None declared.

Auteurs

Hayley Peters (H)

Division of Orthopaedics, Osteoarthritis Research Program, Schroeder Arthritis Institute, University Health Network, Toronto, Ontario, Canada.
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
Krembil Research Institute, University Health Network, Toronto, Ontario, Canada.

Pratibha Potla (P)

Division of Orthopaedics, Osteoarthritis Research Program, Schroeder Arthritis Institute, University Health Network, Toronto, Ontario, Canada.
Krembil Research Institute, University Health Network, Toronto, Ontario, Canada.

Jason S Rockel (JS)

Division of Orthopaedics, Osteoarthritis Research Program, Schroeder Arthritis Institute, University Health Network, Toronto, Ontario, Canada.
Krembil Research Institute, University Health Network, Toronto, Ontario, Canada.

Teodora Tockovska (T)

Division of Orthopaedics, Osteoarthritis Research Program, Schroeder Arthritis Institute, University Health Network, Toronto, Ontario, Canada.
Bioinformatics and HPC Core, Princess Margaret Cancer Research Tower, University Health Network, Toronto, Ontario, Canada.

Chiara Pastrello (C)

Division of Orthopaedics, Osteoarthritis Research Program, Schroeder Arthritis Institute, University Health Network, Toronto, Ontario, Canada.
Krembil Research Institute, University Health Network, Toronto, Ontario, Canada.

Igor Jurisica (I)

Division of Orthopaedics, Osteoarthritis Research Program, Schroeder Arthritis Institute, University Health Network, Toronto, Ontario, Canada.
Krembil Research Institute, University Health Network, Toronto, Ontario, Canada.
Departments of Medical Biophysics and Computer Science, and Faculty of Dentistry, University of Toronto, Toronto, Ontario, Canada.

Keemo Delos Santos (K)

Division of Orthopaedics, Osteoarthritis Research Program, Schroeder Arthritis Institute, University Health Network, Toronto, Ontario, Canada.
Krembil Research Institute, University Health Network, Toronto, Ontario, Canada.

Shabana Vohra (S)

Division of Orthopaedics, Osteoarthritis Research Program, Schroeder Arthritis Institute, University Health Network, Toronto, Ontario, Canada.
Krembil Research Institute, University Health Network, Toronto, Ontario, Canada.

Noah Fine (N)

Division of Orthopaedics, Osteoarthritis Research Program, Schroeder Arthritis Institute, University Health Network, Toronto, Ontario, Canada.
Krembil Research Institute, University Health Network, Toronto, Ontario, Canada.

Starlee Lively (S)

Division of Orthopaedics, Osteoarthritis Research Program, Schroeder Arthritis Institute, University Health Network, Toronto, Ontario, Canada.
Krembil Research Institute, University Health Network, Toronto, Ontario, Canada.

Kim Perry (K)

Division of Orthopaedics, Osteoarthritis Research Program, Schroeder Arthritis Institute, University Health Network, Toronto, Ontario, Canada.
Krembil Research Institute, University Health Network, Toronto, Ontario, Canada.

Nikita Looby (N)

Division of Orthopaedics, Osteoarthritis Research Program, Schroeder Arthritis Institute, University Health Network, Toronto, Ontario, Canada.
Krembil Research Institute, University Health Network, Toronto, Ontario, Canada.
Division of Rheumatology, Psoriatic Arthritis Research Program, Schroeder Arthritis Institute, University Health Network, Toronto, Ontario, Canada.

Sheng Han Li (SH)

Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
Krembil Research Institute, University Health Network, Toronto, Ontario, Canada.
Division of Rheumatology, Psoriatic Arthritis Research Program, Schroeder Arthritis Institute, University Health Network, Toronto, Ontario, Canada.

Vinod Chandran (V)

Division of Orthopaedics, Osteoarthritis Research Program, Schroeder Arthritis Institute, University Health Network, Toronto, Ontario, Canada.
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
Krembil Research Institute, University Health Network, Toronto, Ontario, Canada.
Division of Rheumatology, Psoriatic Arthritis Research Program, Schroeder Arthritis Institute, University Health Network, Toronto, Ontario, Canada.
Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.

Katrina Hueniken (K)

Division of Orthopaedics, Osteoarthritis Research Program, Schroeder Arthritis Institute, University Health Network, Toronto, Ontario, Canada.
Krembil Research Institute, University Health Network, Toronto, Ontario, Canada.

Paramvir Kaur (P)

Division of Orthopaedics, Osteoarthritis Research Program, Schroeder Arthritis Institute, University Health Network, Toronto, Ontario, Canada.
Krembil Research Institute, University Health Network, Toronto, Ontario, Canada.

Anthony V Perruccio (AV)

Division of Orthopaedics, Osteoarthritis Research Program, Schroeder Arthritis Institute, University Health Network, Toronto, Ontario, Canada.
Krembil Research Institute, University Health Network, Toronto, Ontario, Canada.
Department of Surgery, University of Toronto, Toronto, Ontario, Canada.
Institute of Health Policy, Management and Evaluation, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.

Nizar N Mahomed (NN)

Division of Orthopaedics, Osteoarthritis Research Program, Schroeder Arthritis Institute, University Health Network, Toronto, Ontario, Canada.
Krembil Research Institute, University Health Network, Toronto, Ontario, Canada.
Department of Surgery, University of Toronto, Toronto, Ontario, Canada.

Raja Rampersaud (R)

Division of Orthopaedics, Osteoarthritis Research Program, Schroeder Arthritis Institute, University Health Network, Toronto, Ontario, Canada.
Krembil Research Institute, University Health Network, Toronto, Ontario, Canada.
Department of Surgery, University of Toronto, Toronto, Ontario, Canada.

Khalid Syed (K)

Division of Orthopaedics, Osteoarthritis Research Program, Schroeder Arthritis Institute, University Health Network, Toronto, Ontario, Canada.
Krembil Research Institute, University Health Network, Toronto, Ontario, Canada.
Department of Surgery, University of Toronto, Toronto, Ontario, Canada.

Eric Gracey (E)

Molecular Immunology and Inflammation Unit, VIB Centre for Inflammation Research, Ghent University, Ghent, Belgium.
Department of Rheumatology, University Hospital Ghent, Ghent, Belgium.

Roman Krawetz (R)

McCaig Institute for Bone and Joint Health, University of Calgary, Calgary, Alberta, Canada.

Matthew B Buechler (MB)

Department of Immunology, University of Toronto, Toronto, Ontario, Canada.

Rajiv Gandhi (R)

Division of Orthopaedics, Osteoarthritis Research Program, Schroeder Arthritis Institute, University Health Network, Toronto, Ontario, Canada.
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
Krembil Research Institute, University Health Network, Toronto, Ontario, Canada.
Department of Surgery, University of Toronto, Toronto, Ontario, Canada.

Mohit Kapoor (M)

Division of Orthopaedics, Osteoarthritis Research Program, Schroeder Arthritis Institute, University Health Network, Toronto, Ontario, Canada mkapoor@uhnresearch.ca.
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
Krembil Research Institute, University Health Network, Toronto, Ontario, Canada.
Department of Surgery, University of Toronto, Toronto, Ontario, Canada.
ORCID: 0000-0001-9877-0772

Classifications MeSH