The Impact of DDR1 on Bone Material Properties

Abstract

Decreased bone density and deterioration of bone tissue are hallmarks of age-related bone loss. This arises from an imbalance of bone cell regulation, including increased osteoclast (bone-resorbing cell) and decreased osteoblast (bone-forming cell) activity, which collectively affect the collagenous extracellular matrix. Certain cell-surface receptors found in these bone cells can change the content of bone by regulating cell growth and affecting the collagen and mineral content. One such receptor is Discoidin Domain Receptor 1 (DDR1), which binds to collagen type I in bone and affects both matrix mineralization and collagen fibrillogenesis, the effects of which are still being explored. In previous studies we elucidated how lack of DDR1 impaired osteoclast count and increased stiffness in 6-month (mo) murine femurs. This discrepancy, a decrease in bone building cells and an increase in stiffness, may be explained by the underlying matrix environment. In this study we investigated how DDR1 affects the bone collagen and mineral content in 6-mo mice. Femurs were taken from 6-mo female DDR1 knock-out (KO) and wild type (WT) mice. Mid-shaft cortical sections were subjected to Picrosirius Red staining and transmission electron microscopy. To analyze mineral quantity, tissue mineral density, bone mineral density, and thermogravimetric analyses were performed. Our investigations revealed that the DDR1 KO mice had a significant increased mineral percent composition throughout the whole bone matched with a trend towards increase in mineral density in the cortical region. The fibril diameter was enhanced in KO mice while the D-periodicity exhibited no change across genotypes. The collagen fiber packing and size were reduced in the KO model. These results suggest that DDR1 regulates the collagen quality and mineral quantity in the bone, which may in turn regulate bone loss.MARC T34 ProgramA one-year embargo was granted for this item.Academic Major: Mechanical Engineerin