CYBB regulates synovial fibroblast inflammatory activation and sEV-mediated synovial-cartilage communication in osteoarthritis.
8 affiliations
- 1Department of Orthopedics / Central Laboratory, Affiliated Hai'an Hospital of Nantong University, Zhongba Road 17, Hai'an, Jiangsu, 226600, China.
- 2Department of Traumatology and Orthopedics, The Third Affiliated Hospital of Soochow University, The First People's Hospital of Changzhou City, Juqian Road 185, Changzhou City, 213000, China.
- 3Department of Orthopedics, The First Affiliated Hospital of Soochow University, Shizi Street 188, Suzhou, Jiangsu, 215000, China.
- 4Department of Pathology, Affiliated Hai'an Hospital of Nantong University, Zhongba Road 17, Hai'an, Jiangsu, 226600, China.
- 5Department of Orthopedics, the Affiliated Suzhou Hospital of Nanjing Medical University, Guangji Road 242, Suzhou, Jiangsu, 215000, China.
- 6Department of Orthopedics, The First Affiliated Hospital of Soochow University, Shizi Street 188, Suzhou, Jiangsu, 215000, China. [email protected].
- 7Department of Traumatology and Orthopedics, The Third Affiliated Hospital of Soochow University, The First People's Hospital of Changzhou City, Juqian Road 185, Changzhou City, 213000, China. [email protected].
- 8Department of Orthopedics / Central Laboratory, Affiliated Hai'an Hospital of Nantong University, Zhongba Road 17, Hai'an, Jiangsu, 226600, China. [email protected].
Abstract
Objective
Although synovial inflammation is recognized as a factor in the progression of osteoarthritis (OA), the specific role of fibroblast-like synoviocytes (FLS) in cartilage degradation has yet to be fully elucidated. This study sought to identify key regulators that connect inflammatory FLS to chondrocyte dysfunction.Methods
An integrated re-analysis of bulk and single-cell RNA sequencing data from OA synovial tissues was conducted to identify consistently upregulated genes. Functional assays, including migration and invasion tests, were performed on inflammatory FLS. FLS with silenced CYBB expression were co-cultured with chondrocytes to evaluate paracrine effects. small extracellular vesicle (sEV) isolation and tracking were utilized to assess intercellular communication. An OA rat model was employed for in vivo validation through local CYBB knockdown.Results
CYBB expression was markedly upregulated in OA synovium, particularly within inflammatory FLS. Inhibition of CYBB reduced FLS inflammation, migration, and invasion. In co-culture experiments, inflammatory FLS induced chondrocyte inflammation and disrupted matrix gene expression in a manner dependent on CYBB. These effects were mediated by sEVs derived from fibroblast-like synoviocytes (FLS), with their inflammatory cargo being modified through CYBB silencing. In vivo experiments demonstrated that localized suppression of CYBB alleviated synovitis and cartilage degeneration.Conclusions
CYBB serves as a pivotal mediator linking synovial inflammation to cartilage damage in osteoarthritis (OA), by mechanistically regulating the sEV-mediated communication from FLS to chondrocytes. Targeting CYBB could potentially represent a novel therapeutic strategy for OA.
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BibTeX
@article{chen2026cybb,
title = {{CYBB regulates synovial fibroblast inflammatory activation and sEV-mediated synovial-cartilage communication in osteoarthritis.}},
author = {Kai Chen and Xiaoyu Dai and Peizhen Wang and Chuyi Wang and Chang Lv and Huaqiang Tao and Dechun Geng and Wenge Ding and Shujun Lv},
journal = {Arthritis research \& therapy},
year = {2026},
month = jul,
doi = {10.1186/s13075-026-03866-y},
url = {https://europepmc.org/article/MED/42894224},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - CYBB regulates synovial fibroblast inflammatory activation and sEV-mediated synovial-cartilage communication in osteoarthritis.
AU - Kai Chen
AU - Xiaoyu Dai
AU - Peizhen Wang
AU - Chuyi Wang
AU - Chang Lv
AU - Huaqiang Tao
AU - Dechun Geng
AU - Wenge Ding
AU - Shujun Lv
PY - 2026
DA - 2026/07/01
JO - Arthritis research & therapy
DO - 10.1186/s13075-026-03866-y
UR - https://europepmc.org/article/MED/42894224
AB - Objective Although synovial inflammation is recognized as a factor in the progression of osteoarthritis (OA), the specific role of fibroblast-like synoviocytes (FLS) in cartilage degradation has yet to be fully elucidated. This study sought to identify key regulators that connect inflammatory FLS to chondrocyte dysfunction.Methods An integrated re-analysis of bulk and single-cell RNA sequencing data from OA synovial tissues was conducted to identify consistently upregulated genes. Functional assays, including migration and invasion tests, were performed on inflammatory FLS. FLS with silenced CYBB expression were co-cultured with chondrocytes to evaluate paracrine effects. small extracellular vesicle (sEV) isolation and tracking were utilized to assess intercellular communication. An OA rat model was employed for in vivo validation through local CYBB knockdown.Results CYBB expression was markedly upregulated in OA synovium, particularly within inflammatory FLS. Inhibition of CYBB reduced FLS inflammation, migration, and invasion. In co-culture experiments, inflammatory FLS induced chondrocyte inflammation and disrupted matrix gene expression in a manner dependent on CYBB. These effects were mediated by sEVs derived from fibroblast-like synoviocytes (FLS), with their inflammatory cargo being modified through CYBB silencing. In vivo experiments demonstrated that localized suppression of CYBB alleviated synovitis and cartilage degeneration.Conclusions CYBB serves as a pivotal mediator linking synovial inflammation to cartilage damage in osteoarthritis (OA), by mechanistically regulating the sEV-mediated communication from FLS to chondrocytes. Targeting CYBB could potentially represent a novel therapeutic strategy for OA.
SN - 1478-6354
SN - 1478-6362
ER -