TY - JOUR
T1 - How tough is brittle bone? Investigating osteogenesis imperfecta in mouse bone
AU - Carriero, Alessandra
AU - Zimmermann, Elizabeth A.
AU - Paluszny, Adriana
AU - Tang, Simon Y.
AU - Bale, Hrishikesh
AU - Busse, Bjorn
AU - Alliston, Tamara
AU - Kazakia, Galateia
AU - Ritchie, Robert O.
AU - Shefelbine, Sandra J.
PY - 2014/6
Y1 - 2014/6
N2 - The multiscale hierarchical structure of bone is naturally optimized to resist fractures. In osteogenesis imperfecta, or brittle bone disease, genetic mutations affect the quality and/or quantity of collagen, dramatically increasing bone fracture risk. Here we reveal how the collagen defect results in bone fragility in a mouse model of osteogenesis imperfecta (oim), which has homotrimeric α1(I) collagen. At the molecular level, we attribute the loss in toughness to a decrease in the stabilizing enzymatic cross-links and an increase in nonenzymatic cross-links, which may break prematurely, inhibiting plasticity. At the tissue level, high vascular canal density reduces the stable crack growth, and extensive woven bone limits the crack-deflection toughening during crack growth. This demonstrates how modifications at the bone molecular level have ramifications at larger length scales affecting the overall mechanical integrity of the bone; thus, treatment strategies have to address multiscale properties in order to regain bone toughness. In this regard, findings from the heterozygous oim bone, where defective as well as normal collagen are present, suggest that increasing the quantity of healthy collagen in these bones helps to recover toughness at the multiple length scales.
AB - The multiscale hierarchical structure of bone is naturally optimized to resist fractures. In osteogenesis imperfecta, or brittle bone disease, genetic mutations affect the quality and/or quantity of collagen, dramatically increasing bone fracture risk. Here we reveal how the collagen defect results in bone fragility in a mouse model of osteogenesis imperfecta (oim), which has homotrimeric α1(I) collagen. At the molecular level, we attribute the loss in toughness to a decrease in the stabilizing enzymatic cross-links and an increase in nonenzymatic cross-links, which may break prematurely, inhibiting plasticity. At the tissue level, high vascular canal density reduces the stable crack growth, and extensive woven bone limits the crack-deflection toughening during crack growth. This demonstrates how modifications at the bone molecular level have ramifications at larger length scales affecting the overall mechanical integrity of the bone; thus, treatment strategies have to address multiscale properties in order to regain bone toughness. In this regard, findings from the heterozygous oim bone, where defective as well as normal collagen are present, suggest that increasing the quantity of healthy collagen in these bones helps to recover toughness at the multiple length scales.
KW - BONE FRACTURE
KW - BRITTLE BONE
KW - CRACK GROWTH
KW - CRACK INITIATION
KW - FRACTURE MECHANICS
KW - MOUSE BONE
UR - http://www.scopus.com/inward/record.url?scp=84900010719&partnerID=8YFLogxK
U2 - 10.1002/jbmr.2172
DO - 10.1002/jbmr.2172
M3 - Article
C2 - 24420672
AN - SCOPUS:84900010719
SN - 0884-0431
VL - 29
SP - 1392
EP - 1401
JO - Journal of Bone and Mineral Research
JF - Journal of Bone and Mineral Research
IS - 6
ER -