TY - JOUR
T1 - Inflammatory Response of Articular Cartilage to Femoroacetabular Impingement in the Hip
AU - Haneda, Masahiko
AU - Rai, Muhammad Farooq
AU - O’Keefe, Regis J.
AU - Brophy, Robert H.
AU - Clohisy, John C.
AU - Pascual-Garrido, Cecilia
N1 - Publisher Copyright:
© 2020 The Author(s).
PY - 2020/6/1
Y1 - 2020/6/1
N2 - Background: Femoroacetabular impingement (FAI) has been proposed as an etiologic factor in up to 50% of hips with osteoarthritis (OA). Inflammation is thought to be one of the main initiators of OA, yet little is known about the origin of intra-articular inflammation in FAI hips. Hypothesis: Articular cartilage from the impingement zone of patients with FAI has high levels of inflammation, reflecting initial inflammatory process in the hip. Study Design: Controlled laboratory study. Methods: Head-neck cartilage samples were obtained from patients with cam FAI (cam FAI, early FAI; n = 15), advanced OA secondary to cam FAI (FAI OA, late FAI; n = 15), and advanced OA secondary to developmental dysplasia of the hip (DDH OA, no impingement; n = 15). Cartilage procured from young adult donors (n = 7) served as control. Safranin O–stained sections were assessed for cartilage abnormality. Tissue viability was detected by TUNEL assay. Immunostaining of interleukin 1β (IL-1β), catabolic markers (matrix metalloproteinase 13 [MMP-13], a disintegrin and metalloproteinase with thrombospondin motif 4 [ADAMTS-4], aggrecan antibody to C-terminal neoepitope [NITEGE]), and an anabolic marker (type II collagen [COL2]) was performed to evaluate molecular inflammation and metabolic activity. The average percentage of immunopositive cells from the total cell count was calculated. Kruskal-Wallis test followed by Steel-Dwass post hoc test was used for multiple comparisons. Results: Microscopic osteoarthritic changes were more prevalent in cartilage of cam FAI and FAI OA groups compared with DDH OA and control groups. Cartilage in cam FAI and FAI OA groups, versus the DDH group, had higher expression of inflammatory molecules IL-1β (69.7% ± 18.1% and 72.5% ± 13.2% vs 32.7% ± 14.4%, respectively), MMP-13 (79.6% ± 12.6% and 71.4% ± 18.8% vs 38. 5% ± 13.3%), ADAMTS-4 (83.9% ± 12.2% and 82.6% ± 12.5% vs 45.7% ± 15.5%), and COL2 (93.6% ± 3.9% and 92.5% ± 5.8% vs 53.3% ± 21.0%) (P <.001). Expression of NITEGE was similar among groups (cam FAI, 89.7% ± 7.7%; FAI OA, 95.7% ± 4.7%; DDH OA, 93.9% ± 5.2%; P =.0742). The control group had minimal expression of inflammatory markers. Inflammatory markers were expressed in all cartilage zones of early and late FAI but only in the superficial zone of the no impingement group. Conclusion: Cartilage from the impingement zone in FAI is associated with a high expression of inflammatory markers, extending throughout all cartilage zones. Clinical Relevance: Inflammation associated with FAI likely has a deleterious effect on joint homeostasis. Further clinical and translational studies are warranted to assess whether and how surgical treatment of FAI reduces molecular inflammation.
AB - Background: Femoroacetabular impingement (FAI) has been proposed as an etiologic factor in up to 50% of hips with osteoarthritis (OA). Inflammation is thought to be one of the main initiators of OA, yet little is known about the origin of intra-articular inflammation in FAI hips. Hypothesis: Articular cartilage from the impingement zone of patients with FAI has high levels of inflammation, reflecting initial inflammatory process in the hip. Study Design: Controlled laboratory study. Methods: Head-neck cartilage samples were obtained from patients with cam FAI (cam FAI, early FAI; n = 15), advanced OA secondary to cam FAI (FAI OA, late FAI; n = 15), and advanced OA secondary to developmental dysplasia of the hip (DDH OA, no impingement; n = 15). Cartilage procured from young adult donors (n = 7) served as control. Safranin O–stained sections were assessed for cartilage abnormality. Tissue viability was detected by TUNEL assay. Immunostaining of interleukin 1β (IL-1β), catabolic markers (matrix metalloproteinase 13 [MMP-13], a disintegrin and metalloproteinase with thrombospondin motif 4 [ADAMTS-4], aggrecan antibody to C-terminal neoepitope [NITEGE]), and an anabolic marker (type II collagen [COL2]) was performed to evaluate molecular inflammation and metabolic activity. The average percentage of immunopositive cells from the total cell count was calculated. Kruskal-Wallis test followed by Steel-Dwass post hoc test was used for multiple comparisons. Results: Microscopic osteoarthritic changes were more prevalent in cartilage of cam FAI and FAI OA groups compared with DDH OA and control groups. Cartilage in cam FAI and FAI OA groups, versus the DDH group, had higher expression of inflammatory molecules IL-1β (69.7% ± 18.1% and 72.5% ± 13.2% vs 32.7% ± 14.4%, respectively), MMP-13 (79.6% ± 12.6% and 71.4% ± 18.8% vs 38. 5% ± 13.3%), ADAMTS-4 (83.9% ± 12.2% and 82.6% ± 12.5% vs 45.7% ± 15.5%), and COL2 (93.6% ± 3.9% and 92.5% ± 5.8% vs 53.3% ± 21.0%) (P <.001). Expression of NITEGE was similar among groups (cam FAI, 89.7% ± 7.7%; FAI OA, 95.7% ± 4.7%; DDH OA, 93.9% ± 5.2%; P =.0742). The control group had minimal expression of inflammatory markers. Inflammatory markers were expressed in all cartilage zones of early and late FAI but only in the superficial zone of the no impingement group. Conclusion: Cartilage from the impingement zone in FAI is associated with a high expression of inflammatory markers, extending throughout all cartilage zones. Clinical Relevance: Inflammation associated with FAI likely has a deleterious effect on joint homeostasis. Further clinical and translational studies are warranted to assess whether and how surgical treatment of FAI reduces molecular inflammation.
KW - cartilage degeneration
KW - femoroacetabular impingement
KW - inflammation
KW - osteoarthritis
UR - http://www.scopus.com/inward/record.url?scp=85084823754&partnerID=8YFLogxK
U2 - 10.1177/0363546520918804
DO - 10.1177/0363546520918804
M3 - Article
C2 - 32383968
AN - SCOPUS:85084823754
SN - 0363-5465
VL - 48
SP - 1647
EP - 1656
JO - American Journal of Sports Medicine
JF - American Journal of Sports Medicine
IS - 7
ER -