Lipoxygenase Gene Regulates Bone Mineral Density

Researchers have discovered that the Alox15 gene, which codes for the enzyme 12/15-lipoxygenase, is a key regulator of bone mineral density in a mouse model that mimics human osteoporosis.

Investigators at Oregon Health and Science University (Portland, USA) worked with a population of mice with low bone mineral density (BMD) that was a genetic model for osteoporosis in humans. Through crossbreeding and genome analysis they identified the lipoxygenase gene Alox15 as a negative regulator of peak bone mineral density. Alox15 encodes the enzyme 12/15-lipoxygenase that converts fatty acids into ligands, for the peroxisome proliferator-activated receptor-gamma (PPARg). Results published in the January 9, 2003, issue of Science showed that drugs that inhibited the activity of 12/15-lipoxygenase improved bone density and strength in two rodent models of osteoporosis.

"We compared the pattern of gene expression in C57BL/6 and DBA/2 mice, to identify the responsible gene,” explained first author Dr. Robert F. Klein, associate professor of medicine at Oregon Health and Science University. "Microarray (gene-chip) analysis indicated that Alox15 was the only differentially expressed gene within our region on chromosome 11. Between 60% and 80% of natural variations in bone density is genetically determined, and understanding this gene's importance in normal skeletal physiology is a goal of bone and mineral research. This is a major step forward.”





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