Distinct Pattern of Inflammation of Articular Cartilage and the Synovium in Early and Late Hip Femoroacetabular Impingement

Abstract

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.

Gene expression and histological studies of articular chondrocytes in cam-type femoroacetabular impingement demonstrates chronic and sustained inflammation and age related abnormal extracellular matrix

“…Considering the gene expression of SOX9, Collagen 2 and aggrecan in FAI tissue was lower than normal tissue, the metabolism of the cells in FAI tissue was considered even lower than normal cartilage tissue. This conclusion is in contrast with the report from Haneda et al 17 In their study, they also found increased inflammatory factors in FAI tissue. They considered it was due to a metabolic hyperactivity of the cells.…”

“…Haneda et al reported the viability of the cells in FAI tissue was similar among early, late stages FAI and normal cartilage. 7,17 Their results suggested no extensive cell apoptosis in FAI tissues.…”

“…Handeda et al also distinguished FAI patients to two groups, early and late stages. 7,17 In their report, late stage FAI represented OA that had already developed in the hip joint. Age was also one of the significant differences between two groups in their study.…”

Genes associated with inflammation and bone remodeling are highly expressed in the bone of patients with the early-stage cam-type femoroacetabular impingement

“…The metabolic changes were heightened by mechanical impingemen t[ 13 ]. The hip cartilage in patients with FAI has been reported to exhibit an OA phenotype in those with early-stage FAI, similar to that observed in patients with hip OA secondary to FA I[ 12 ]. All recent studies on the pathogenesis and pathologic process of hip OA caused by FAI focused on the cartilage or the synovial membrane.…”

“…The articular cartilage from the impingement zone of the hips with FAI is known to express higher levels of certain markers of inflammation and degeneratio n[ 6 , 9 – 12 ]. Hashimoto et al .…”