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Abstract
IntroductionIn ankylosing spondylitis (AS), joint remodeling leading to joint ankylosis involves cartilage fusion. Here, we analyzed whether chondrocyte hypertrophy is involved in cartilage fusion and subsequent joint remodeling in AS.MethodsWe assessed the expression of chondrocyte hypertrophy markers runt-related transcription factor 2 (Runx2), type X collagen (COL10), matrix metalloproteinase 13 (MMP13), osteocalcin and beta-catenin and the expression of positive bone morphogenic proteins (BMPs) and negative regulators (dickkopf-1 (DKK-1)), sclerostin, (wingless inhibitory factor 1 (wif-1)) of chondrocyte hypertrophy in the cartilage of facet joints from patients with AS or osteoarthritis (OA) and from autopsy controls (CO) by immunohistochemistry. Sex determining region Y (SRY)-box 9 (Sox9) and type II collagen (COL2) expression was assessed as indicators of chondrocyte integrity and function.ResultsThe percentage of hypertrophic chondrocytes expressing Runx2, COL10, MMP13, osteocalcin or beta-catenin was significantly increased in OA but not in AS joints compared to CO joints. Frequencies of sclerostin-positive and DKK-1-positive chondrocytes were similar in AS and CO. In contrast, wif-1- but also BMP-2- and BMP-7-expressing and Sox9-expressing chondrocytes were drastically reduced in AS joints compared to CO as well as OA joints whereas the percentage of COL2-expressing chondrocytes was significantly higher in AS joints compared to CO joints.ConclusionsWe found no evidence for chondrocyte hypertrophy within hyaline cartilage of AS joints even in the presence of reduced expression of the wnt inhibitor wif-1 suggesting that chondrocyte hypertrophy is not a predominant pathway involved in joint fusion and remodeling in AS. In contrast, the reduced expression of Sox9, BMP-2 and BMP-7 concomitantly with induced COL2 expression rather point to disturbed cartilage homeostasis promoting cartilage degeneration in AS.
Highlights
In ankylosing spondylitis (AS), joint remodeling leading to joint ankylosis involves cartilage fusion
No increased percentage of hypertrophic chondrocytes expressing runt-related transcription factor 2 (Runx2), type X collagen (COL10) or matrix metalloproteinase 13 (MMP13) within the hyaline articular cartilage in AS facet joints While the number of chondrocytes expressing Runx2, COL10 and MMP13 was significantly increased in OA facet joints compared to autopsy controls (CO) (Runx2 = 33.1 ± 18.1 %, COL10 = 4.9 ± 4.9 %, MMP13 = 1.4 ± 0.9 %), no increased frequencies of Runx2, COL10- and MMP13-expressing chondrocytes were found in joints of AS patients (Runx2 = 40.0 ± 23.5 %, COL10 = 2.7 ± 3.2 %, MMP13 = 1.9 ± 2.6 %; Fig. 1a–c)
No evidence for stage-dependent induction of chondrocyte hypertrophy To determine if occurrence of chondrocyte hypertrophy is restricted to distinct stages of facet joint remodeling, which we have recently described [4], we performed a subanalysis of AS joints grouped according to the proposed stages
Summary
In ankylosing spondylitis (AS), joint remodeling leading to joint ankylosis involves cartilage fusion. We analyzed whether chondrocyte hypertrophy is involved in cartilage fusion and subsequent joint remodeling in AS. Ankylosing spondylitis (AS) is a chronic inflammatory disease primarily affecting the sacroiliac joints and the spine [1]. Our histomorphometric study as well as a study in which we performed computed tomography (CT) scans of the facet, i.e., zygapophyseal joints provided no evidence for a major contribution of capsular ankylosis or extraarticular osteophytes in AS facet joints [4]. The coincidental occurrence of a subchondral fibrous tissue, which carried bone-destructive features, with cartilaginous joint fusion suggested a major contribution of this tissue to the remodeling process
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