TYPE-I COLLAGEN MUTATION COMPROMISES THE POST-YIELD BEHAVIOR OF MOV13LONG-BONE

Despite recent advances in our understanding of the molecular basis of skeletal fragility little is known about how these molecular alterati ons lead to whole bone brittleness. In the current study, we investiga ted the relationship between a type-I collagen mutation and post-yield behavior of whole bone in Mov13 transgenic mice by considering tissue -level organizational issues known to be important for normal bone fra cture. Mechanical assays revealed that the post-yield deflection of Mo v13 femurs was reduced by 61% relative to littermate controls. Fractog raphic images revealed that lamellar interfaces, which were important for dissipating energy during the failure process of control femurs, w ere not effective in Mov13 mice. Further investigation revealed that a 22% reduction in bone collagen content, a 2-fold increase in tissue p orosity, and significant alterations in collagen organization interfer ed with normal energy dissipation mechanisms of Mov13 microstructure. Collectively, the results provided the first evidence that the reduced ductility associated with a type-I collagen mutation was mediated by alterations in intermediate structures that normally contribute to the post-yield behavior of cortical bone. The results suggest that, to be tter understand the pathogenesis of skeletal fragility, it is importan t to consider the effects of molecular alterations on higher-level str uctures, particularly those structures that contribute to the failure mechanisms in normal bone.