1. Britney Stewart Dr. Evans
Genetics of Osteoporosis: Can a New Perspective of Osteoporosis Lead to New Treatments?
Britney Stewart
Dr. Evans

2. Osteoporosis
Osteoporosis is a disease that causes deterioration of the bone and bone tissue and low bone mineral density (BMD)
Environmental factors influence osteoporosis susceptibility but it is believed that BMD is genetically influenced as well

3. Suspect Genes
Polymorphisms in numerous genes could control Osteoporosis
the VDR gene
LRP5 and SOST gene
TNFSF11 gene
ESR1 gene

4. Identification Large-scale genome wide association studies (GWAS)
scans the entire genome to locate genes that are associated with the disease
Candidate gene approach
identify pre-specified genetic loci that contribute to the risk for osteoporosis
Twin/family studies
those with effected lineages have genomes screened to find linkages between certain chromosomes and osteoporosis-related genes

5. VDR Vitamin D Receptor Regulates calcium homeostasis in the bone
Single nucleotide polymorphisms (SNPs) in intron 8 and the 3’- untranslated region are associated with a lower BMD

6. LRP5 and SOST Key players in the Wnt signaling pathway
Wnt signaling pathway regulates bone density through the LRP5
The Wnt protein and a frizzled receptor interact with LRP5 to initiate Wnt β-catenin signaling 
β-catenin moves to the nucleus to attach to transcription factors
Activation of this pathway leads to an increase in bone formation
When SOST is present the Wnt protein is unable to interact with LRP5 and a decrease in bone formation occurs

7. Wnt Signaling Pathway (Urano & Inoue)

8. LRP5 Protein Structure (Urano & Inoue)

9. TNFSF11 Encodes RANK receptor and RANKL protein
RANK receptor on osteoclasts and osteoclast precursors
regulate differentiation and function
RANKL is the protein that interacts with RANK
Stimulates bone resorption by activating RANK signaling and promotes maturation of pre-osteoclasts
Polymorphisms regulate but their mechanisms are still being investigated

10. ESR1
Estrogen 1 receptor
Correlation between BMD and the variable number of repeats (VNTR) within the ESR1 promoter regions (Urano & Inoue)
Presence of polymorphisms result in osteoporosis
Urano, Inoue Genetics of osteoporosis. Biochem Bioph Res Co 452: