Distinct Transcriptional Responses to 17β-Estradiol in Human Meniscal Fibrochondrocytes from a Female and a Male Donor
- 1Department of Neurosciences and Psychiatry, College of Medicine and Life Sciences, The University of Toledo, Toledo, OH 43614, USA
- 2Department of Orthopaedic Surgery, College of Medicine and Life Sciences, The University of Toledo, Toledo, OH 43614, USA
- 3ProMedica, Toledo, OH 43604, USA
Abstract
Osteoarthritis (OA) affects women more often than men, and estrogen has been implicated in joint homeostasis, yet its effects on meniscal fibrochondrocytes (MFCs) remain poorly defined. We reanalyzed a public RNA sequencing dataset (Gene Expression Omnibus, GSE199087) of MFCs from two age-matched donors, one female and one male (both 47 years old). Cells from each donor were treated in triplicate with pulsed 17β-estradiol (E2, 240 µM for 1 h every 24 h over 72 h) or vehicle control. Differential expression was assessed with limma-voom, and pathways were identified with Gene Set Enrichment Analysis (GSEA), Enrichr, and iLINCS, retaining only Gene Ontology terms supported by all three. In the female donor’s cells, E2 upregulated DNA replication and cell-cycle pathways and lowered MMP1, MMP2, IL12A, and MYD88. In the male donor’s cells, E2 upregulated chromatin remodeling and developmental signaling pathways, with NOTCH1 among the leading-edge genes, and downregulated antigen presentation pathways and mitochondrial genes. At the gene level, some changes were shared by both donors, including lower TIMP1. Because each sex was represented by one donor, these differences cannot be attributed to sex with confidence. The findings are hypothesis-generating and identify candidate pathways for validation in larger, sex-balanced cohorts.
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BibTeX
@article{yu2026distinct,
title = {{Distinct Transcriptional Responses to 17β-Estradiol in Human Meniscal Fibrochondrocytes from a Female and a Male Donor}},
author = {Youngmin Yu and John Vergis and Hunter M. Eby and Mario Markho and Jonathan Kopacz and Kayla Cartwright and Michael Hershey and Jiayong Liu and Robert E. McCullumsmith},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = nov,
doi = {10.3390/ijms27219881},
url = {https://www.mdpi.com/1422-0067/27/21/9881},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Distinct Transcriptional Responses to 17β-Estradiol in Human Meniscal Fibrochondrocytes from a Female and a Male Donor
AU - Youngmin Yu
AU - John Vergis
AU - Hunter M. Eby
AU - Mario Markho
AU - Jonathan Kopacz
AU - Kayla Cartwright
AU - Michael Hershey
AU - Jiayong Liu
AU - Robert E. McCullumsmith
PY - 2026
DA - 2026/11/04
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27219881
UR - https://www.mdpi.com/1422-0067/27/21/9881
AB - Osteoarthritis (OA) affects women more often than men, and estrogen has been implicated in joint homeostasis, yet its effects on meniscal fibrochondrocytes (MFCs) remain poorly defined. We reanalyzed a public RNA sequencing dataset (Gene Expression Omnibus, GSE199087) of MFCs from two age-matched donors, one female and one male (both 47 years old). Cells from each donor were treated in triplicate with pulsed 17β-estradiol (E2, 240 µM for 1 h every 24 h over 72 h) or vehicle control. Differential expression was assessed with limma-voom, and pathways were identified with Gene Set Enrichment Analysis (GSEA), Enrichr, and iLINCS, retaining only Gene Ontology terms supported by all three. In the female donor’s cells, E2 upregulated DNA replication and cell-cycle pathways and lowered MMP1, MMP2, IL12A, and MYD88. In the male donor’s cells, E2 upregulated chromatin remodeling and developmental signaling pathways, with NOTCH1 among the leading-edge genes, and downregulated antigen presentation pathways and mitochondrial genes. At the gene level, some changes were shared by both donors, including lower TIMP1. Because each sex was represented by one donor, these differences cannot be attributed to sex with confidence. The findings are hypothesis-generating and identify candidate pathways for validation in larger, sex-balanced cohorts.
SN - 1422-0067
ER -