Published in:
Annals of the Rheumatic Diseases, 76 (2017) 2, Seite 442-449
Language:
English
DOI:
10.1136/annrheumdis-2016-209319
ISSN:
1468-2060;
0003-4967
Origination:
Footnote:
Description:
ObjectiveInterterritorial regions of articular cartilage matrix are rich in decorin, a small leucine-rich proteoglycan and important structural protein, also involved in many signalling events. Decorin sequesters transforming growth factor β (TGFβ), thereby regulating its activity. Here, we analysed whether increased bioavailability of TGFβ in decorin-deficient (Dcn−/−) cartilage leads to changes in biomechanical properties and resistance to osteoarthritis (OA).MethodsUnchallenged knee cartilage was analysed by atomic force microscopy (AFM) and immunohistochemistry. Active transforming growth factor β-1 (TGFβ1) content within cultured chondrocyte supernatants was measured by ELISA. Quantitative real-time (RT)-PCR was used to analyse mRNA expression of glycosaminoglycan (GAG)-modifying enzymes in C28/I2 cells following TGFβ1 treatment. In addition, OA was induced inDcn−/−and wild-type (WT) mice via forced exercise on a treadmill.ResultsAFM analysis revealed a strikingly higher compressive stiffness inDcn−/−than in WT cartilage. This was accompanied by increased negative charge and enhanced sulfation of GAG chains, but not by alterations in the levels of collagens or proteoglycan core proteins. In addition, decorin-deficient chondrocytes were shown to release more active TGFβ1. Increased TGFβ signalling led to enhancedChst11sulfotransferase expression inducing an increased negative charge density of cartilage matrix. These negative charges might attract more water resulting in augmented compressive stiffness of the tissue. Therefore, decorin-deficient mice developed significantly less OA after forced exercise than WT mice.ConclusionsOur study demonstrates that the disruption of decorin-restricted TGFβ signalling leads to higher stiffness of articular cartilage matrix, rendering joints more resistant to OA. Therefore, the loss of an important structural component can improve cartilage homeostasis.