Session Type: Abstract Submissions (ACR)
Osteoproliferation leading to joint ankylosis is a characteristic feature of ankylosing spondylitis (AS). In general, there are two ways of bone formation: a) endochondral bone formation via generation of collagen X scaffolds requiring hypertrophic chondrocytes and b) membraneous or direct bone formation mediated by osteoblasts without primary cartilage synthesis.
Using zygapophyseal joints of AS patients (and zygapophyseal joints from autopsy controls and from OA patients for comparison) , we determined whether chondrocytes acquire signs of chondrocyte hypertrophy upon joint remodeling or whether direct ossification by osteoblasts could be involved in the process of new bone formation in AS.
17 zygapophyseal, i.e. facet joints from 14 patients with AS fulfilling the modified New York Criteria, 22 zygapophyseal joints from 12 patients with OA and 11 zygapophyseal joints of 10 non-AS control patients were included in the study.
The percentage of hypertrophic chondrocytes was determined by immunohistochemistry according to Runx2, MMP13 and collagen X expression in the cartilage of zygapophyseal joints. Activation of the wingless (wnt) pathway controlling chondrocyte hypertrophy was analyzed according to beta-catenin expression. Osteoblasts were identified according to CD56 staining.
The percentage of hypertrophic chondrocytes expressing Runx2, COL10 and MMP13 was significantly increased in OA (mean ± SEM: Runx2 = 55.03 ± 11.83%, COL10 = 8.79 ± 8.88%, MMP13 = 14.55 ± 8.77%) but not in AS joints (Runx2 = 38.49 ± 22.84%, COL10 = 2.71 ± 3.05%, MMP13 = 1.80 ± 2.53%) compared to CO joints (Runx2 = 33.06 ± 17.27%, COL10 = 4.87 ± 4.66%, MMP13 = 1.43 ± 0.87%). Beta-catenin expression was low in AS (0.54 ± 0.84%) and CO zygapophyseal joints (1.83 ± 2.85% of chondrocytes) while in OA joints the number of beta-catenin positive chondrocytes was significantly increased (18.84 ± 18.31%).
Osteoblasts were observed at their typical location, i.e. within the bone marrow, lining the trabecular bone. However, CD56-positive cells were also found at the edges of fibrous tissue which is often observed at subchondral bone marrow sites in AS and OA joints and which invades the subchondral bone. Runx-2 and weak osteocalcin expression of these lining cells further supports their osteoblastic nature. Ossification of cartilage was predominantly found at contact zones between the fibrous tissue and the cartilage in AS joints; i.e. in 71% of AS joints and 27% of OA joints with fibrous tissue-cartilage contacts.
The lack of chondrocyte hypertrophy as an indicator of endochondral bone formation but co-localization of osteoblasts with fibrous tissue and bony transformation at contact zones to cartilage in AS joints suggest that direct ossification is involved in joints ankylosis in AS.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/in-situ-analysis-of-mechanisms-of-new-bone-formation-in-zygapophyseal-joints-from-patients-with-ankylosing-spondylitis/