title: Forced exercise-induced osteoarthritis is attenuated in mice lacking the small leucine-rich proteoglycan decorin.
abstract: OBJECTIVE
  Interterritorial 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).
  
  
  METHODS
  Unchallenged 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 in Dcn-/-and wild-type (WT) mice via forced exercise on a treadmill.
  
  
  RESULTS
  AFM analysis revealed a strikingly higher compressive stiffness in Dcn-/-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 enhanced Chst11 sulfotransferase 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.
  
  
  CONCLUSIONS
  Our 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.
authors.affiliation: Institute of Experimental Musculoskeletal Medicine, University Hospital Münster, Münster, Germany.|Institute of Physiological Chemistry and Pathobiochemistry, University of Münster, Münster, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Gronau
authors.affiliation: Institute of Sports Medicine, Justus-Liebig University Giessen, Giessen, Germany.
authors.forename: Karsten
authors.initials: K
authors.lastname: Krüger
authors.affiliation: Center for Applied Tissue Engineering and Regenerative Medicine (CANTER), Munich University of Applied Sciences and Center for Nanoscience (CeNS), Munich, Germany.
authors.forename: Carina
authors.initials: C
authors.lastname: Prein
authors.affiliation: Laboratory of Experimental Surgery and Regenerative Medicine, Department of General, Trauma and Reconstruction Surgery, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: Attila
authors.initials: A
authors.lastname: Aszodi
authors.affiliation: Institute of Physiological Chemistry and Pathobiochemistry, University of Münster, Münster, Germany.
authors.forename: Isabel
authors.initials: I
authors.lastname: Gronau
authors.affiliation: Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, USA.
authors.forename: Renato V
authors.initials: RV
authors.lastname: Iozzo
authors.affiliation: Institute of Sports Medicine, Justus-Liebig University Giessen, Giessen, Germany.
authors.forename: Frank C
authors.initials: FC
authors.lastname: Mooren
authors.affiliation: Center for Applied Tissue Engineering and Regenerative Medicine (CANTER), Munich University of Applied Sciences and Center for Nanoscience (CeNS), Munich, Germany.
authors.forename: Hauke
authors.initials: H
authors.lastname: Clausen-Schaumann
authors.affiliation: Institute of Experimental Musculoskeletal Medicine, University Hospital Münster, Münster, Germany.|Department of Orthopaedic Surgery, Otto-von-Guericke University, Magdeburg, Germany.
authors.forename: Jessica
authors.initials: J
authors.lastname: Bertrand
authors.affiliation: Institute of Experimental Musculoskeletal Medicine, University Hospital Münster, Münster, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Pap
authors.affiliation: Institute of Physiological Chemistry and Pathobiochemistry, University of Münster, Münster, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Bruckner
authors.affiliation: Institute of Physiological Chemistry and Pathobiochemistry, University of Münster, Münster, Germany.
authors.forename: Rita
authors.initials: R
authors.lastname: Dreier
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D001696:Biomechanical Phenomena; D002358:Cartilage, Articular / Q000378:metabolism*; D058575:Decorin / Q000235:genetics* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D006025:Glycosaminoglycans / Q000378:metabolism; D007150:Immunohistochemistry; D051379:Mice; D018345:Mice, Knockout; D018625:Microscopy, Atomic Force; D010003:Osteoarthritis / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D010805:Physical Conditioning, Animal / Q000009:adverse effects / Q000379:methods*; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D016212:Transforming Growth Factor beta / Q000378:metabolism* / Q000494:pharmacology
chemical_list: C546879:Dcn protein, mouse; D058575:Decorin; D006025:Glycosaminoglycans; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta
keywords: Chondrocytes; Cytokines; Knee Osteoarthritis