Progesterone Modulates Protein Synthesis in Osteoarthritic Fibroblast-like Synoviocytes
9 affiliations
- 1Department of Pharmacology, Institute of Neuroscience and Physiology, University of Gothenburg, 41390 Gothenburg, Sweden
- 2SportsMed, Carlanderska Hospital, 40545 Gothenburg, Sweden
- 3Department of Orthopedics, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, 41390 Gothenburg, Sweden
- 4Department of Rheumatology and Inflammation, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 41346 Gothenburg, Sweden
- 5Bioinformatics and Data Centre, Sahlgrenska Academy, University of Gothenburg, 41390 Gothenburg, Sweden
- 6Proteomics Core Facility, SciLifeLab, Sahlgrenska Academy, University of Gothenburg, 41390 Gothenburg, Sweden
- 7Department of Endocrinology, Sahlgrenska University Hospital, University of Gothenburg, 41345 Gothenburg, Sweden
- 8National Institute of Research and Development in Technical Physics, 700050 Iasi, Romania
- 9Orthopedics and Trauma Clinic, County Emergency Hospital, 700111 Iasi, Romania
Abstract
Knee osteoarthritis (OA) is highly prevalent in women and is characterized by structural joint alterations and synovial inflammatory processes that contribute to pain and impaired mobility. In a previous study, we identified a positive correlation between progesterone levels and pain intensity in postmenopausal women. However, the role of progesterone in synovial inflammation remains poorly understood. Therefore, this study aimed to characterize sex-specific differences in synovial tissue between postmenopausal women and age-matched men and to investigate the association between progesterone levels and the identified molecular profile. Whole blood and synovial tissue were collected from women and men with knee OA to assess plasma progesterone concentrations and the proteomic profiles of synovial tissue and isolated primary fibroblast-like synoviocytes (FLSs). The expression and localization of progesterone receptors were evaluated using RNAscope and immunofluorescence. FLS stimulated with physiological concentrations of progesterone were used for de novo protein synthesis assays. Quantitative proteomics of synovial tissue revealed enrichment of protein synthesis-related pathways in women compared to age-matched men, and isolated FLS from women with knee OA exhibited a pro-inflammatory and pro-fibrotic proteomic profile. Stratification by plasma progesterone levels identified two distinct patient groups, where lower progesterone levels were associated with pro-inflammatory signatures. The RNAscope analysis demonstrated increased transcriptional activity in synovial tissue from women with knee OA, localized to CD90+ sublining FLS. However, progesterone receptor expression at both the RNA and protein levels showed no sex-specific differences. Moreover, physiological concentrations of progesterone inhibited de novo protein synthesis in FLS isolated from men with knee OA. These findings underscore the hormonal context-dependent modulatory effects of progesterone on synovial inflammation and fibroblast activity. The study further highlights the importance of incorporating sex-specific hormonal profiles into OA patient stratification to support more precise and targeted therapeutic strategies.
Related
- Targeting the NLRP3 inflammasome in rheumatoid arthritis fibroblast-like synoviocytes: pathogenic mechanisms, therapeutic strategies, and translational perspectives
- Sanguinarine ameliorates rheumatoid arthritis by activating the Hippo-YAP/TAZ pathway to induce apoptosis and suppress inflammation in fibroblast-like synoviocytes
- Fibroblast-like synoviocytes exacerbate autoimmune arthritis upon psychological stress in an IL-6–dependent manner
- JQ1 Inhibits the Hyperproliferation and Aggressiveness of Fibroblast-Like Synoviocytes in Rheumatoid Arthritis via Regulating IL7R.
- Microenvironment-Triggered Sequentially Targeted Micelles for Dual Regulation of Macrophages and Fibroblast-Like Synoviocytes via ROS-Responsive Rg1 Release and HAP-1-Mediated Celastrol Delivery in Rheumatoid Arthritis Therapy.
BibTeX
@article{askar2026progesterone,
title = {{Progesterone Modulates Protein Synthesis in Osteoarthritic Fibroblast-like Synoviocytes}},
author = {Fadi Askar and Georgios Chatziagorou and Sofia Wüstenhagen and Alessia Capraro and Björn Andersson and Evelin Berger and Daniela Esposito and Luminita Labusca and Carmen Corciulo},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27198899},
url = {https://www.mdpi.com/1422-0067/27/19/8899},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Progesterone Modulates Protein Synthesis in Osteoarthritic Fibroblast-like Synoviocytes
AU - Fadi Askar
AU - Georgios Chatziagorou
AU - Sofia Wüstenhagen
AU - Alessia Capraro
AU - Björn Andersson
AU - Evelin Berger
AU - Daniela Esposito
AU - Luminita Labusca
AU - Carmen Corciulo
PY - 2026
DA - 2026/10/07
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27198899
UR - https://www.mdpi.com/1422-0067/27/19/8899
AB - Knee osteoarthritis (OA) is highly prevalent in women and is characterized by structural joint alterations and synovial inflammatory processes that contribute to pain and impaired mobility. In a previous study, we identified a positive correlation between progesterone levels and pain intensity in postmenopausal women. However, the role of progesterone in synovial inflammation remains poorly understood. Therefore, this study aimed to characterize sex-specific differences in synovial tissue between postmenopausal women and age-matched men and to investigate the association between progesterone levels and the identified molecular profile. Whole blood and synovial tissue were collected from women and men with knee OA to assess plasma progesterone concentrations and the proteomic profiles of synovial tissue and isolated primary fibroblast-like synoviocytes (FLSs). The expression and localization of progesterone receptors were evaluated using RNAscope and immunofluorescence. FLS stimulated with physiological concentrations of progesterone were used for de novo protein synthesis assays. Quantitative proteomics of synovial tissue revealed enrichment of protein synthesis-related pathways in women compared to age-matched men, and isolated FLS from women with knee OA exhibited a pro-inflammatory and pro-fibrotic proteomic profile. Stratification by plasma progesterone levels identified two distinct patient groups, where lower progesterone levels were associated with pro-inflammatory signatures. The RNAscope analysis demonstrated increased transcriptional activity in synovial tissue from women with knee OA, localized to CD90+ sublining FLS. However, progesterone receptor expression at both the RNA and protein levels showed no sex-specific differences. Moreover, physiological concentrations of progesterone inhibited de novo protein synthesis in FLS isolated from men with knee OA. These findings underscore the hormonal context-dependent modulatory effects of progesterone on synovial inflammation and fibroblast activity. The study further highlights the importance of incorporating sex-specific hormonal profiles into OA patient stratification to support more precise and targeted therapeutic strategies.
SN - 1422-0067
ER -