Pattern of Inflammatory Molecules in Cartilage of the Impingement Zone in FAI Hips Suggests Origin of Hip Degeneration

Abstract

Objectives:

Femoroacetabular impingement (FAI) is considered a common cause of articular cartilage damage and early hip osteoarthritis (OA) in the young-adult patients. Molecular inflammation is believed to be one of the main initiators of hip OA. Matrix metalloproteinase (MMP)-13 and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-4 are known to function as extracellular matrix degrading enzymes in OA joints and have been shown to increase during the process of OA onset. Interleukin (IL)-1β is considered one of the key cytokines involved in the pathogenesis of OA. The aim of this study is to characterize inflammation and early OA pathways in cartilage from the head-neck impingement area in patients with symptomatic FAI cam.

Methods:

Cartilage samples were obtained in the head neck-junction area from 37 patients undergoing hip surgery between May 2017 and July 2018. Nine patients had a clinical diagnosis of FAI cam (FAI cam) and 15 patients presented advanced OA secondary to FAI cam (OA FAI). These cartilage samples were compared to cartilage samples obtained from similar head neck-junction area from 13 patients with advanced OA secondary to developmental dysplasia of the hip with no impingement (OA DDH). Radiographically, the α-angle was utilized to confirm hip impingement. All histological sections were stained with Safranin-O to assess cartilage degeneration. OARSI grade and Mankin score were used to quantify degenerative OA changes. Immunohistochemistry was performed for IL-1β, MMP-13 and ADAMTS-4. Quantification of immunopositive cells was performed in a blinded fashion. One-way analysis of variance with Tukey’s post hoc test was applied to analyze differences between three groups.

Results:

FAI cam patients were significantly younger than OA FAI patients (p<0.001) and OA DDH patients (p=0.0461) (Table 1). The average α-angle was significantly higher in the FAI cam and OA FAI groups than the OA DDH group (p<0.001). Cartilage samples from the FAI cam and the OA FAI groups showed degenerative changes. The average OARSI grade was significantly (p<0.01) higher in FAI cam (4.0±0.4) and OA FAI (3.6±0.9) compared to OA DDH (2.2±0.6). The average Mankin score was significantly (p<0.001) higher in FAI cam (7.6±1.2) and OA FAI (6.9±1.8) than OA DDH (4.1±0.7). IL-1β was expressed in cartilage samples from all groups, although the pattern varied.IL-1β was expressed mainly in the superficial layer in the OA DDH group but throughout all cartilage layers in the FAI cam and OA FAI groups. The % immunopositive cells were significantly (p<0.001) higher in FAI cam (58.1±8.9) and OA FAI (71.3±12.4) than OA DDH (28.9±6.3). Similar pattern of distribution was observed for MMP-13 (72.7±11.3, 70.2±18.2 vs 38.0±8.6; p<0.001, p<0.001) and ADAMTS-4 (73.1±7.3, 82.0±12.3 vs 45.3±12.7; p<0.001, p<0.001) (Figure 1).

Conclusion:

Osteoarthritic changes are evident in the cartilage from the head-neck area of patients with FAI cam morphology. Inflammatory molecules were evident in both early and late stages of hip impingement, suggesting the head-neck impingement area is a potential mediator of inflammation and joint degeneration.

Figure 1:

Safranin-O staining and immunohistochemistry of the cartilage from FAI cam or head-neck junction area. The arrows show the layer of immunopositive cells on each panel. Bar Graph representing OARSI grade, Mankin score, immunopositive cells (%) of IL-1β immunopositive cells (%) of MMP-13, and immunopositive cells (%) of ADAMTS-4 between groups. Statistical difference was observed between groups. Scale bar = 500µm.

Table 1.

Patients data and radiographic characteristics

	OA DDH	OA FAI	FAI cam	p value
number	13	15	9
age (years)	49.23 ± 8.16	56.57 ± 7.17	32.67 ± 10.30	p < 0.001
sex	1 male, 12 females	13 males, 2 females	8 males, 1 female
BMI (kg/m2)	28.5 ± 5.9	31.42 ± 6.12	30.18 ± 2.69	0.778
α-angle (deg)	44.05 ± 6.48	84.2 ± 11.54	76.75 ± 9.68	p < 0.001
procedure	13 total hip arthroplasty	15 total hip arthroplasty	6 hip arthroscopy,3 surgical dislocation

OA: osteoarthritis, BMI: body mass index, FAI, femoroacetabular impingement.