Abstract
Collagen is the major structural component of cartilage and mutations in the genes encoding Type XI collagen are associated with severe skeletal dysplasias including Fibrochondrogenesis and Stickler syndrome, and with early onset osteoarthritis. Using a zebrafish mutant for col11a2 we test the impact of loss of Type XI collagen on cell behaviour and mechanical performance in the developing skeleton. We show that in col11a2 mutants Type II collagen is made but is prematurely lost from maturing cartilage and ectopically expressed in the joint. Using Atomic Force Microscopy, we show that skeletal tissues (cartilage and bone) are stiffer in mutant zebrafish. We also observe wider joints with less defined interzones in mutants, which impacts on the function of the joint. Using Finite Element Analyses we model the mechanical performance of wild type and mutant joint shape and material properties; demonstrating that changing joint shape has a greater impact on the pattern of skeletal strain than material properties. Finally, we show that heterozygous carriers of the col11a2 mutation reach adulthood but are susceptible to severe, early onset, osteoarthritis. Taken together our data demonstrates a key role for Type XI collagen in maintaining the properties of cartilage matrix; which when lost leads to alterations to cell behaviour that give rise to joint pathologies.
