615 - A Transcriptomic Analysis of Cartilage-synovium Crosstalk in the Transition from Hip Femoroacetabular Impingement to Osteoarthritis Highlights Neuroregulatory Pathways as Key Drivers of Hip Osteoarthritis Progression

Thursday, February 19, 2026

5:00 PM - 6:30 PM AST

Presenting Author(s)

CA

Chengchong Ai, MD

Postdoctoral Research Associate
Washington University in St. Louis
SAINT LOUIS, Missouri, United States

Corresponding Author(s)

CP

Cecilia Pascual-Garrido, MD

Associate Professor
Washington University in St. Louis
St.Louis, Missouri, United States

Co-Author(s)

JL

Jiachen Liu, MBBS

Visiting researcher
Washington University in St. Louis
St.Louis, Missouri, United States

Submitter(s)

CA

Chengchong Ai, MD

Postdoctoral Research Associate
Washington University in St. Louis
SAINT LOUIS, Missouri, United States

Objectives: Hip osteoarthritis (OA) is a common degenerative joint disease causing substantial socioeconomical burden worldwide. Femoroacetabular impingement (FAI) is a common pre-arthritic condition of the hip that contributes to up to 50% of hip osteoarthritis (OA) cases and represents a critical window for early intervention. The molecular crosstalk between cartilage and synovium during the FAI-to-OA transition remains poorly characterized. Elucidating these mechanisms has important implications for early intervention and function-oriented management strategies. Here, the objective of this study is to define shared biological programs across cartilage and synovium in FAI and OA patients using integrative transcriptomic analysis, with a particular focus on neuroregulatory pathways.

Design:
Cartilage and synovium specimens were collected intraoperatively from FAI and OA patients (cartilage: n=4 FAI, n=12 OA; synovium: n=4 FAI, n=4 OA) for bulk RNA sequencing.

Results:
Integration across tissue types identified 123 concordantly upregulated and 25 concordantly downregulated genes in OA versus FAI, reflecting shared pathophysiologic reprogramming. Functional enrichment of these co-dysregulated genes highlighted distinct yet complementary biological processes, with strong convergence on neuroregulatory pathways, including myelination, synaptic signaling, axon guidance, and neuronal differentiation. Gene set enrichment analysis (GSEA) confirmed elevated activity of neurodevelopmental and synaptic remodeling pathways in OA. To further explore the systems-level organization of neural signatures, we performed weighted gene co-expression network analysis (WGCNA) in both tissues. Based on network centrality, module membership, gene significance, and neural pathway annotation, we prioritized a group of top-ranked candidate drivers, potentially orchestrating cartilage-synovium communication during OA progression.

Conclusions:
We found neural pathways were involved in the pathological dialogue between cartilage and synovium. This may underlie both structural deterioration and pain sensitization in the development from FAI to OA. These findings not only improve our understanding of joint-level disease mechanisms but also nominate novel candidates for therapeutic targeting in the pre-OA stage.