Event
BIOE Seminar: Transcriptomic Profiling and Human Tissue-on-Chip Modeling of Synoviocytes in Femo...
Friday, May 8, 2026
9:00 a.m.
A. James Clark Hall, Room #2121
Catherine Kuo
ckk@umd.edu
Chia-Lung Wu
University of Rochester Medicine
Transcriptomic Profiling and Human Tissue-on-Chip Modeling of Synoviocytes in Femoroacetabular Impingement and Hip Osteoarthritis
Abscract
Femoroacetabular impingement (FAI) and synovitis are key drivers of hip osteoarthritis (OA), yet the synovial cellular and molecular mechanisms underlying disease progression remain poorly defined. Here, we integrated single-cell RNA sequencing with spatial transcriptomics to profile synovial tissues from sex-matched FAI and hip OA patients (n = 6 per group), enabling high-resolution mapping of disease-specific cellular states and interactions. Compared to FAI, hip OA synovium exhibited a pronounced expansion of epiregulin (EREG)-enriched lining fibroblast-like synoviocytes (FLS), characterized by a pro-inflammatory phenotype with elevated CXCL1, IL8, and MMP expression. Trajectory analysis suggests that EREG+ FLS arise from DPP4+PI16+ sublining FLS, potentially regulated by NFIX and REL in FAI and by ELK3 and ETV6 in OA. Notably, we identified a critical fibroblast growth factor 2 (FGF2) - syndecan-4 (SDC4) signaling axis between COL1A1+ fibrotic macrophages and EREG+ FLS, which may drive IL6, IL8, and MMP1 expression and promote inflammatory and angiogenic pathways in OA. Using a human tissue-on-a-chip model, we further demonstrate that FGF2 stimulation increases IL6 production in EREG+ FLS, whereas FGF2 neutralization or SDC4 inhibition attenuates this response. Together, these findings define a disease-specific synovial niche and highlight the FGF2-SDC4 axis as a promising therapeutic target for hip OA.
Bio
Dr. Chia-Lung Wu earned his Bachelor’s degree in Materials Science and Engineering from National Taipei University of Technology and his Master’s degree from National Taiwan University. He received his Ph.D. in Biomedical Engineering from Duke University in 2015. Dr. Wu then completed his postdoctoral training at Washington University in St. Louis before beginning his faculty career in 2020. He is currently an Assistant Professor in the Department of Orthopaedics and the Center for Musculoskeletal Research (CMSR) at the University of Rochester. His research focuses on elucidating the molecular mechanisms by which genetic and epigenetic regulators control the development, homeostasis, and disease progression of musculoskeletal tissues, with particular emphasis on cartilage biology and osteoarthritis.
