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Molecular Characterization of Articular Cartilage from Young Adults with Femoroacetabular Impingement

Hashimoto, Shingo MD, PhD; Rai, Muhammad Farooq PhD; Gill, Corey S. MD; Zhang, Zhiqi MD; Sandell, Linda J. PhD; Clohisy, John C. MD

Journal of Bone & Joint Surgery - American Volume: 21 August 2013 - Volume 95 - Issue 16 - p 1457–1464
doi: 10.2106/JBJS.L.00497
Scientific Articles
Supplementary Content

Background: Femoroacetabular impingement is a frequent cause of hip pain and may lead to secondary osteoarthritis, yet little is known about the molecular events linking mechanical hip impingement and articular cartilage degeneration. The first goal of this study was to quantify the expression of inflammatory cytokine and chemokine, matrix-degrading, and extracellular matrix genes in articular cartilage harvested from control hips and hips with femoroacetabular impingement and end-stage osteoarthritis. The second goal was to analyze the relative expression of these genes in articular cartilage harvested at various stages of osteoarthritis.

Methods: Cartilage samples were obtained from thirty-two hips undergoing hip preservation surgery for femoroacetabular impingement or hip arthroplasty. Three control cartilage samples were also analyzed. Specimens were graded intraoperatively with regard to the severity of cartilage damage, the radiographic osteoarthritis grade was recorded, and quantitative RT-PCR (real-time polymerase chain reaction) was performed to determine relative gene expression.

Results: Except for interleukin-1β (IL-1β) and CXCL2, the mRNA (messenger RNA) expression of all other chemokine (IL-8, CXCL1, CXCL3, CXCL6, CCL3, and CCL3L1), matrix-degrading (matrix metalloproteinase [MMP]-13 and ADAMTS-4), and structural matrix (COL2A1 [collagen, type II, alpha] and ACAN [aggregan]) genes was higher overall in cartilage from hips with femoroacetabular impingement compared with hips with osteoarthritis and normal controls. The differences reached significance (p ≤ 0.05) for seven of these ten quantified genes, with CXCL3, CXCL6, and COL2A1 being elevated in the femoroacetabular impingement group compared with only the control group and IL-8, CCL3L1, ADAMTS-4, and ACAN being elevated compared with both the osteoarthritis and control groups. When samples were grouped according to the stage of the degenerative cascade, mRNA expression was relatively higher in one of the two middle stages of femoroacetabular impingement (chondromalacia or cleavage/thinning), with the difference reaching significance for IL-8, CXCL2, CXCL3, CCL3L1, and ACAN. ACAN expression was diminished in hips with osteoarthritis compared with femoroacetabular impingement but elevated compared with the control articular cartilage.

Conclusions: Articular cartilage from the impingement zone of hips with femoroacetabular impingement (and particularly those hips in the cleavage/thinning stage) expressed higher levels of certain inflammatory, anabolic, and catabolic genes, representing a heightened metabolic state.

Clinical Relevance: The articular cartilage from the impingement zone of hips with femoroacetabular impingement was metabolically hyperactive, supporting the concept that such impingement is a structural precursor to hip osteoarthritis.

1Department of Orthopaedic Surgery, Washington University School of Medicine at Barnes-Jewish Hospital, 660 South Euclid Avenue, Box 8233, St. Louis, MO 63110. E-mail address for S. Hashimoto: E-mail address for M.F. Rai: E-mail address for C.S. Gill: E-mail address for Z. Zhang: E-mail address for L.J. Sandell: E-mail address for J.C. Clohisy:

Copyright 2013 by The Journal of Bone and Joint Surgery, Incorporated
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