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. 2015 Jul 17;17(1):170.
doi: 10.1186/s13075-015-0675-5.

Cartilage in Facet Joints of Patients With Ankylosing Spondylitis (AS) Shows Signs of Cartilage Degeneration Rather Than Chondrocyte Hypertrophy: Implications for Joint Remodeling in AS

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Cartilage in Facet Joints of Patients With Ankylosing Spondylitis (AS) Shows Signs of Cartilage Degeneration Rather Than Chondrocyte Hypertrophy: Implications for Joint Remodeling in AS

Janine Bleil et al. Arthritis Res Ther. .
Free PMC article

Abstract

Introduction: In 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.

Methods: We 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.

Results: The 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.

Conclusions: We 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.

Figures

Fig. 1
Fig. 1
No increased percentage of hypertrophic chondrocytes expressing Runx2, COL10 or MMP13 within the hyaline articular cartilage in ankylosing spondylitis facet joints. The percentage of positively stained chondrocytes among all chondrocytes [%] and representative immunohistochemical staining of Runx2 (a), COL10 (b), MMP13 (c) and osteocalcin (d) within the hyaline articular cartilage of facet joints from controls (CO; A–D upper pictures), patients with ankylosing spondylitis (AS; A–D middle pictures) and osteoarthritis (OA; A–D lower pictures); original magnification 40× and 400×; ns = not significant p >0.05; ***= p <0.001; **= p <0.01, *= p <0.05. COL10 type X collagen, MMP matrix metalloproteinase, Runx2, runt-related transcription factor 2
Fig. 2
Fig. 2
No evidence for stage-dependent induction of chondrocyte hypertrophy. Representative immunohistochemical staining of safranin-O/light green (a) from facet joints of patients with ankylosing spondylitis with open joints (AS stage I), with cartilaginous fused joints (AS stage II) and with bony fused joints (AS stage III). Representative immunohistochemical staining and percentage of chondrocytes that were positive for Runx2 (b), MMP13 (c) and COL10 (d) within the hyaline articular cartilage of facet joints from patients with AS stage I (B–D first column), AS stage II (B–D second column) and AS stage III (B–D third column); original magnification 40× and 400×; dashed line indicates the median of the control group. COL10 type X collagen, MMP matrix metalloproteinase, Runx2, runt-related transcription factor 2
Fig. 3
Fig. 3
No activation of the wnt pathway in chondrocytes according to beta-catenin staining in ankylosing spondylitis facet joints. Percentage of positively stained chondrocytes [%] and representative immunohistochemical staining of beta-catenin (a), wif-1 (b), DKK-1 (c) and sclerostin (d) in the hyaline articular cartilage of facet joints from controls (CO; A–D upper pictures), patients with ankylosing spondylitis (AS; A–D middle pictures) and osteoarthritis (OA; A–D lower pictures); original magnification 40× and 400×; ns = not significant p >0.05; ***= p <0.001; **= p <0.01. COL10 type X collagen, DKK-1 dickkopf-1, wif-1 wingless inhibitor factor-1, wnt wingless
Fig. 4
Fig. 4
Reduced expression of chondrocyte growth factors within the cartilage of ankylosing spondylitis facet joints. Percentage of positively stained chondrocytes among all chondrocytes [%] and representative immunohistochemical staining of BMP-2 (a) and BMP-7 (b) within the hyaline articular cartilage of facet joints from controls (CO; A–B upper pictures), patients with ankylosing spondylitis (AS; A–B middle pictures) and osteoarthritis (OA; A–B lower pictures); original magnification 40× and 400×; ns = not significant p >0.05; ***= p <0.001; *= p <0.05. BMP bone morphogenic protein
Fig. 5
Fig. 5
Reduced Sox9 expression but increased COL2 expression in ankylosing spondylitis facet joints. Percentage of positively stained chondrocytes among all chondrocytes [%] and representative immunohistochemical staining of Sox9 (a) and COL2 (b) within the hyaline articular cartilage of facet joints from controls (CO; A–B upper pictures), patients with ankylosing spondylitis (AS; A–B middle pictures) and osteoarthritis (OA; A–B lower pictures); original magnification 40× and 400×; ns = not significant p >0.05; ***= p <0.001; *= p <0.05. COL2 type II collagen, Sox9 sex determining region Y (SRY)-box 9

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References

    1. Braun J, Sieper J. Ankylosing spondylitis. Lancet. 2007;369:1379–1390. doi: 10.1016/S0140-6736(07)60635-7. - DOI - PubMed
    1. de Vlam K, Mielants H, Veys EM. Involvement of the zygapophyseal joint in ankylosing spondylitis: relation to the bridging syndesmophyte. J Rheumatol. 1999;26:1738–1745. - PubMed
    1. Ball J. The enthesopathy of ankylosing spondylitis. Br J Rheumatol. 1983;22:25–28. doi: 10.1093/rheumatology/XXII.suppl_2.25. - DOI - PubMed
    1. Bleil J, Maier R, Hempfing A, Schlichting U, Appel H, Sieper J, et al. Histomorphological and histomorphometric characteristics of zygapophyseal joint remodelling in ankylosing spondylitis. Arthritis Rheumatol. 2014;66:1745–1754. doi: 10.1002/art.38404. - DOI - PubMed
    1. Francois RJ, Gardner DL, Degrave EJ, Bywaters EG. Histopathologic evidence that sacroiliitis in ankylosing spondylitis is not merely enthesitis. Arthritis Rheum. 2000;43:2011–2024. doi: 10.1002/1529-0131(200009)43:9<2011::AID-ANR12>3.0.CO;2-Y. - DOI - PubMed

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