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
