**IL-1** β **Damages Fibrocartilage and Upregulates MMP-13 Expression in Fibrochondrocytes in the Condyle of the Temporomandibular Joint**

**Hessam Tabeian 1,**†**, Beatriz F. Betti 1,2,3,**†**, Cinthya dos Santos Cirqueira 4, Teun J. de Vries 5, Frank Lobbezoo 2, Anouk V. ter Linde 1, Behrouz Zandieh-Doulabi 1, Marije I. Koenders 6, Vincent Everts 1 and Astrid D. Bakker 1,\***


4 Núcleo de Anatomia Patológica, Instituto Adolfo Lutz, São Paulo 01246-000, Brazil; cinthyaquiron@gmail.com


† These authors contributed equally to this work.

Received: 14 April 2019; Accepted: 1 May 2019; Published: 7 May 2019

**Abstract:** The temporomandibular joint (TMJ), which di ffers anatomically and biochemically from hyaline cartilage-covered joints, is an under-recognized joint in arthritic disease, even though TMJ damage can have deleterious e ffects on physical appearance, pain and function. Here, we analyzed the effect of IL-1β, a cytokine highly expressed in arthritic joints, on TMJ fibrocartilage-derived cells, and we investigated the modulatory e ffect of mechanical loading on IL-1β-induced expression of catabolic enzymes. TMJ cartilage degradation was analyzed in 8–11-week-old mice deficient for IL-1 receptor antagonist (IL-1RA−/−) and wild-type controls. Cells were isolated from the juvenile porcine condyle, fossa, and disc, grown in agarose gels, and subjected to IL-1β (0.1–10 ng/mL) for 6 or 24 h. Expression of catabolic enzymes (ADAMTS and MMPs) was quantified by RT-qPCR and immunohistochemistry. Porcine condylar cells were stimulated with IL-1β for 12 h with IL-1β, followed by 8 h of 6% dynamic mechanical (tensile) strain, and gene expression of MMPs was quantified. Early signs of condylar cartilage damage were apparent in IL-1RA−/− mice. In porcine cells, IL-1β strongly increased expression of the aggrecanases ADAMTS4 and ADAMTS5 by fibrochondrocytes from the fossa (13-fold and 7-fold) and enhanced the number of MMP-13 protein-expressing condylar cells (8-fold). Mechanical loading significantly lowered (3-fold) IL-1β-induced MMP-13 gene expression by condylar fibrochondrocytes. IL-1β induces TMJ condylar cartilage damage, possibly by enhancing MMP-13 production. Mechanical loading reduces IL-1β-induced MMP-13 gene expression, suggesting that mechanical stimuli may prevent cartilage damage of the TMJ in arthritic patients.

**Keywords:** ADAMTS4; ADAMTS5; fossa; cartilage degradation; arthritis; mechanical loading; MMP-13; IL1β; temporomandibular joint; juvenile idiopathic arthritis

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