title: Interleukin-1β enhances cartilage-to-cartilage integration.
abstract: The failure of cartilages to fuse, particularly in the case of articular cartilage under conditions of repair is due to morphological and structural constraints of the tissue. Factors that impede integration include, non-vascularisation, low cellularity, and proteoglycan in the surrounding extracellular matrix acting as a natural barrier to cellular migration. We hypothesised that brief activation of a catabolic cascade by cytokines followed by culture under anabolic conditions would promote tissue fusion in a ring-disk model of cartilage integration. Our results show that transient exposure to 10 ng mL(-1) interleukin-1β, followed by two weeks post-culture under anabolic conditions, enhanced cartilage-cartilage integration compared to untreated explants. Quantitative PCR analysis of catabolism-related genes ADAMTS4 and MMP13 showed both were transiently upregulated and these findings correlated with evidence of extracellular matrix remodelling. At the level of histology, we observed chondrocytes readily populated the interfacial matrix between fused explants in interleukin-1β treated explants, whereas in control explants this region was relatively acellular in comparison. Catabolic cytokine treated explants exhibited 29-fold greater adhesive strength (0.859 MPa versus 0.028 MPa, P 〈 0.05) than untreated counterparts. Collectively, our results demonstrate that a single short catabolic pulse followed by an anabolic response is sufficient to generate mechanically robust, integrative cartilage repair.
authors: School of Biosciences, Cardiff University, Museum Avenue, Cardiff CF10 3AX, Wales, UK. smbimk@cardiff.ac.uk
authors: I M
authors: IM
authors: Khan
authors: L G
authors: LG
authors: Gonzalez
authors: L
authors: L
authors: Francis
authors: R S
authors: RS
authors: Conlan
authors: S J
authors: SJ
authors: Gilbert
authors: S K
authors: SK
authors: Singhrao
authors: D
authors: D
authors: Burdon
authors: A P
authors: AP
authors: Hollander
authors: V C
authors: VC
authors: Duance
authors: C W
authors: CW
authors: Archer
mesh_terms: D051722:ADAM Proteins / Q000235:genetics / Q000378:metabolism; D000071121:ADAMTS4 Protein; D000818:Animals; D002358:Cartilage, Articular / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D002417:Cattle; D019902:Chondrocytes / Q000378:metabolism; D006025:Glycosaminoglycans / Q000032:analysis; D053583:Interleukin-1beta / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D053509:Matrix Metalloproteinase 13 / Q000235:genetics / Q000378:metabolism; D011348:Procollagen N-Endopeptidase / Q000235:genetics / Q000378:metabolism; D014945:Wound Healing / Q000502:physiology*
chemical_list: D006025:Glycosaminoglycans; D053583:Interleukin-1beta; D051722:ADAM Proteins; D053509:Matrix Metalloproteinase 13; D011348:Procollagen N-Endopeptidase; D000071121:ADAMTS4 Protein