Differences in articular hip cartilage gene expression between femoroacetabular impingement (FAI) and end-stage hip osteoarthritis. Issue 7 (31st July 2020)

• Record Type: Journal Article
• Authors: Reuter, John; Soles, Gillian; Ackert-Bicknell, Cheryl; Giordano, Brian; Kuhns, Benjamin
• Is Part Of: Orthopaedic journal of sports medicine. Volume 8:Issue 7(2020)Supplement 6
• Publication Date: 2020-07-31
• Subjects: Sports medicine -- Periodicals; Orthopedics -- Periodicals; Arthroscopy -- Periodicals; Arthroplasty -- Periodicals; Knee -- Surgery -- Periodicals; 616.7
• DOI: 10.1177/2325967120S00396
• Languages: English
• ISSNs: 2325-9671

Abstract

Objectives: The morphological deformities in Femoroacetabular Impingement (FAI) have been associated with hip osteoarthritis (OA), however the molecular mechanisms for OA initiation and progression are poorly understood. The purpose of this study was to use whole genome RNA sequencing to characterize differences in gene expression articular cartilage samples isolated from patients undergoing surgery for FAI and idiopathic OA. We hypothesized that there would be significant differences in genes expression in pathways related to inflammation as well as cartilage and bone turnover. Methods: 20 patients undergoing either hip arthroscopy for FAI (5 male, 5 female) or total hip arthroplasty (5 male, 5 female) for end-stage osteoarthritis were included in the study. FAI patients required a Cam deformity with an Alpha Angle greater than 55 while patients with dysplasia (LCEA<25) or prior hip surgery were excluded. Exclusion criteria for the THA cohort included dysplasia, and post-traumatic OA or inflammatory OA. Cartilage samples were obtained over the Cam deformity prior to femoroplasty in the FAI group or over anterosuperior femoral head-neck junction in the OA group following extraction of the femoral head. Following RNA isolation, Next Generation RNA sequencing was performed to evaluate gene expression. Differential expression data was incorporated into the Ingenuity Pathway Analysis (IPA) platform to identify differences in canonical signaling pathways associated with osteoarthritis. Results: There were 3531 genes that were significantly differentially expressed between the FAI and OA cohorts. Of these, there were 27 genes that were upregulated by a greater than 2 log-fold change in the OA cohort and 524 genes that were upregulated by a greater than 2 log-fold change in the FAI cohort. There was significant differential expression in genes related to cartilage metabolism (Table 1) and canonical osteoarthritis pathways involving BMP, TGFβ, and Wnt signaling. (Table 2). Additionally, FAI samples had significant upregulation of EGF-ERBB mediated signaling which compared to osteoarthritic tissue. Conclusion: The results of the present study support our hypothesis that there are significant differences in gene expression between FAI and OA samples in multiple pathways that are implicated in osteoarthritis. Osteoarthritis samples had increased expression of cartilage breakdown and inflammation while femoroacetabular impingement samples had greater expression of chondroprotective genes. Further study of cartilage samples from FAI patients may provide insight into the molecular mechanisms of osteoarthritis progression. Table 1. Differential gene expression in genes related to cartilage metabolism. Osteoarthritic samples had elevated COL10, 24, 8, and 9 genes while FAI had elevated COMP, COL4, and COL6 genes. Cartilage Metabolism Upregulated OA Padj Upregulated FAI Padj COL10A1 0.0001638 COMP 0.034951 COL24A1 0.0117991 COL4A3 5.96E-33 COL8A1 0.0274064 COL4A4 9.46E-14 COL9A1 0.0004479 COL4A5 1.49E-14 COL9A2 0.0090092 COL6A6 9.56E-05 ADAMTS4 0.0003928 COL6A6 2.23E-08 Table 2. Differential expression of genes previously implicated in osteoarthritis. Osteoarthritis samples had elevated markets of end stage cartilage breakdown (ADAMTS4, MMP13, TNF) while FAI samples had increased expression of chondroprotective genes (FGF18, WNT 16, BMPR18) Canonical Osteoarthritis Pathway Upregulated OA Upregulated FAI GREM1 3.32E-12 SMAD4 0.002188 MMP1 3.24E-05 C/EBP 2.32E-04 COL10A1 1.64E-04 WNT16 0.001925 FRZB 3.32E-08 PGC1 2.11E-07 MMP13 2.77E-04 FGF18 9.67E-09 MATN3 0.00205 VEGFD 1.03E-12 MMP3 0.007351 SOX10 0.000216 ADAMTS4 3.93E-04 NOS1 1.87E-34 Osteopontin 0.006119 DKK2 0.007801 MMP9 0.004763 GDF6 1.08E-07 S1PR3 0.003633 BMPR1B 1.31E-22 TNF 0.001382 RUNX2 1.19E-04 SPHK1 8.83E-05 TGFB1 3.44E-04 CTR 0.012398 RANK 3.77E-06