A human rheumatoid arthritis bone–cartilage interface organoid recapitulates bone, cartilage, and immune interactions
- 1Department of Biological Sciences, Seton Hall University, South Orange, NJ 07079 USA
- 2Department of Orthopaedics, Rutgers New Jersey Medical School, 90 Bergen Street, Suite 7300, Newark, NJ 07101 USA
- 3Scottsdale, AZ United States
Abstract
Background: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial inflammation, cartilage degradation, and bone erosion. Fibroblast-like synoviocytes (FLS) play a central role in perpetuating joint damage, yet current therapies inadequately address FLS-driven pathology. Existing preclinical models, including murine collagen-induced arthritis and conventional in vitro cultures, lack the complexity to fully recapitulate human disease mechanisms.
Methods: Here, we describe the development of a three-dimensional (3D) RA bone–cartilage interface (BCI) organoid that integrates primary human mesenchymal stem cell-derived osteoblasts, peripheral blood mononuclear cell-derived osteoclasts and lymphocytes, immortalized human chondrocyte spheroids, and the RA synovial fibroblast cell line SW982.
Results: Exposure to TNF-α, IL-1β, and TGF-β induced pro-inflammatory cytokines, matrix-degrading enzymes, and increased fibrotic gene expression, accompanied by histological and microCT evidence of bone dysregulation. Therapeutic testing showed that methotrexate, etanercept, and tofacitinib reduced cytokine production and pro-inflammatory gene expression but had limited impact on profibrotic gene expression.
Conclusions: This modular, human-derived RA BCI organoid reproduced key features of RA pathogenesis that can enable direct assessment of therapeutic mechanisms at the bone–cartilage–synovial interface. The RA BCI organoid provides a physiologically relevant, scalable platform for preclinical drug discovery and for identifying combination strategies that address both the inflammatory and fibrotic components of RA pathology.
Graphical Abstract:
Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s41232-026-00439-z.
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BibTeX
@article{adams2026human,
title = {{A human rheumatoid arthritis bone–cartilage interface organoid recapitulates bone, cartilage, and immune interactions}},
author = {Mary Adams and Christopher Grieg and Waldemar Gonsiorek and Charlene Wetterstrand and J. Patrick O’Connor and Jessica Cottrell},
journal = {Inflammation and Regeneration},
year = {2026},
month = aug,
doi = {10.1186/s41232-026-00439-z},
url = {https://doi.org/10.1186/s41232-026-00439-z},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - A human rheumatoid arthritis bone–cartilage interface organoid recapitulates bone, cartilage, and immune interactions
AU - Mary Adams
AU - Christopher Grieg
AU - Waldemar Gonsiorek
AU - Charlene Wetterstrand
AU - J. Patrick O’Connor
AU - Jessica Cottrell
PY - 2026
DA - 2026/08/08
JO - Inflammation and Regeneration
DO - 10.1186/s41232-026-00439-z
UR - https://doi.org/10.1186/s41232-026-00439-z
AB - Background: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial inflammation, cartilage degradation, and bone erosion. Fibroblast-like synoviocytes (FLS) play a central role in perpetuating joint damage, yet current therapies inadequately address FLS-driven pathology. Existing preclinical models, including murine collagen-induced arthritis and conventional in vitro cultures, lack the complexity to fully recapitulate human disease mechanisms. Methods: Here, we describe the development of a three-dimensional (3D) RA bone–cartilage interface (BCI) organoid that integrates primary human mesenchymal stem cell-derived osteoblasts, peripheral blood mononuclear cell-derived osteoclasts and lymphocytes, immortalized human chondrocyte spheroids, and the RA synovial fibroblast cell line SW982. Results: Exposure to TNF-α, IL-1β, and TGF-β induced pro-inflammatory cytokines, matrix-degrading enzymes, and increased fibrotic gene expression, accompanied by histological and microCT evidence of bone dysregulation. Therapeutic testing showed that methotrexate, etanercept, and tofacitinib reduced cytokine production and pro-inflammatory gene expression but had limited impact on profibrotic gene expression. Conclusions: This modular, human-derived RA BCI organoid reproduced key features of RA pathogenesis that can enable direct assessment of therapeutic mechanisms at the bone–cartilage–synovial interface. The RA BCI organoid provides a physiologically relevant, scalable platform for preclinical drug discovery and for identifying combination strategies that address both the inflammatory and fibrotic components of RA pathology. Graphical Abstract: Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s41232-026-00439-z.
SN - 1880-9693
SN - 1880-8190
ER -