Title: Bone Strength in TLR4 Pathway Deficient Mice

Bones are formed from a combination of collagen and minerals, primarily calcium and phosphate salts. One of the cells in bone is the osteoclast that resorb (i.e., remove) preexisting bone, a process essential for bone development and adaptability. This cell belongs to the macrophage lineage of cells, and has its origin in the marrow. In diseases such as osteoporosis, the healthy balance of adult bone adaptability is altered and there is more bone resorption than formation, resulting in a net deficit of bone. Receptor proteins like Myeloid differentiation factor 88 (MyD88), Cluster of differentiation 14 (CD14) and (according to Wikipedia) TIR-domaincontaining adapter-Inducing interferon –β (Trif) allows the Toll-like-receptors (TLRs) of the innate immune system to maintain the proper immune function in the body. These innate immune system proteins also may play a role in the differentiation and proliferation of osteoclasts, the cells that resorb (i.e., remove) bone. The mouse strain C3H HeJ has defective TLR4. Interestingly, they have much thicker cortices in their long bones and higher bone mineral content than other mice strains without such defects. In the current studies, we will assess the relationship between components of the TLR4 pathway genes and the development of bone strength and material properties.