Distinct Pattern of Inflammation of Articular Cartilage and the Synovium in Early and Late Hip Femoroacetabular Impingement
Authors: Haneda Masahiko , Rai Muhammad Farooq , Cai Lei , Brophy Robert H. , O’Keefe Regis J. , Clohisy John C. , Pascual-Garrido Cecilia 
Published: August 2020

Background: The molecular mechanism of how femoroacetabular impingement (FAI) morphology leads to hip osteoarthritis (OA) is yet to be determined. The expression and location of inflammation-related molecules during early- and late-stage FAI have not been previously described. Moreover, the characterization of intra-articular inflammation away from the cam deformity as well as the nature of adjacent synovial tissue have also not been extensively reported. Hypothesis: Early-stage FAI has a similar expression of inflammation-related markers in the head-neck and acetabular cartilage but less synovitis than late-stage FAI. Study Design: Controlled laboratory study. Methods: Head-neck cartilage, acetabular cartilage, and synovial samples were obtained from patients undergoing hip preservation surgery for the treatment of symptomatic cam FAI (early FAI group; n = 15) and advanced OA secondary to cam FAI (late FAI group; n = 15). Samples procured from healthy young adult donors served as the control group (n = 7). Cartilage degeneration was assessed by histology, and the expression of inflammation-related proteins (interleukin–1 beta [IL-1β], matrix metalloproteinase–13 [MMP-13], a disintegrin and metalloproteinase with thrombospondin motifs–4 [ADAMTS-4], type II collagen [COL2], and aggrecan neoepitope [NITEGE]) was measured by immunostaining. Synovial samples in the early and late FAI groups were examined for synovitis and the expression of IL-1β. Results: Head-neck cartilage in the early FAI group showed significantly more degeneration than the control group and an increased expression of inflammation-related proteins (IL-1β: 69.7% ± 18.1% vs 20.2% ± 4.9%, respectively; MMP-13: 79.6% ± 12.6% vs 25.3% ± 9.5%; ADAMTS-4: 83.9% ± 12.2% vs 24.3% ± 11.1%; NITEGE: 89.7% ± 7.7% vs 39.8% ± 20.5%) ( P < .001). Head-neck and acetabular cartilage in the early and late FAI groups showed a similar degree of degeneration. Moreover, a similar expression of inflammation-related proteins was observed between the early and late FAI groups for head-neck cartilage (IL-1β: 69.7% ± 18.1% vs 72.5% ± 13.2%; MMP-13: 79.6% ± 12.6% vs 71.4% ± 18.8%; ADAMTS-4: 83.9% ± 12.2% vs 82.6% ± 12.5%; COL2: 93.6% ± 3.9% vs 92.5% ± 5.8%; NITEGE: 89.7% ± 7.7% vs 95.7% ± 4.7%) and acetabular cartilage (IL-1β: 83.3% ± 24.8% vs 80.7% ± 15.6%; MMP-13: 94.3% ± 9.7% vs 85.2% ± 12.3%; ADAMTS-4: 98.5% ± 2.3% vs 98.4% ± 3.4%; COL2: 99.8% ± 0.7% vs 99.7% ± 1.1%; NITEGE: 96.7% ± 6.7% vs 99.2% ± 2.2%). In contrast, synovitis was minimal with a low expression of IL-1β in the early FAI group compared with the late FAI group. Conclusion: Hip cartilage exhibited an OA phenotype in patients with early-stage FAI, similar to what was observed in hip OA secondary to FAI. Severe synovitis was only evident with late-stage FAI. Clinical Relevance: This study supports the concept that early hip impingement is associated with cartilage degeneration and catabolism.