cks bone formation locally. At the same time, orexins interact with orexin receptor 2 (OX2R) in the brain. In this case, the interaction reduces the circulating levels of leptin, a hormone known to decrease bone mass, and thereby promotes bone formation. Therefore, osteoporosis prevention and treatment may be achieved by either inhibiting OX1R or activating OX2R.
"We were very intrigued by this yin-yang-style dual regulation," said Dr. Wan, a member of the Cecil H. and Ida Green Center for Reproductive Biology Sciences and UT Southwestern's Harold C. Simmons Comprehensive Cancer Center. "It is remarkable that orexins manage to regulate bone formation by using two different receptors located in two different tissues."
The central nervous system regulation through OX2R, and therefore promotion of bone formation, was actually dominant over regulation through OX1R. So when the group examined mice lacking both OX1R and OX2R, they had very fragile bones with decreased bone formation. Similarly, when they assessed mice that expressed high levels of orexins, those mice had increased numbers of osteoblasts and enhanced bone formation.
The research was done in collaboration with Dr. Masashi Yanagisawa, Adjunct Professor of Molecular Genetics at UT Southwestern, a Howard Hughes Medical Institute investigator, and now with the International Institute for Integrative Sleep Medicine at the University of Tsukuba, in Japan. Dr. Yanagisawa's laboratory discovered orexins in 1998.
Other UT Southwestern researchers include lead author Dr. Wei Wei, postdoctoral researcher in Pharmacology; Dr. Xian-Jin Xie, Associate Professor of Clinical Sciences and the Simmons Cancer Center; Dr. Toshiyuki Motoike, Assistant Professor of Molecular Genetics; and Drs. Jing Y. Krzeszinski and Zixue Jin, postdoctoral researchers in Pharmacology.
The work was supported by the UT Southwestern Endowed Scholar Startup Fund, the National Institutes of Health, the Welch Foundation, the Howard Hughes Medical Institute, and the Japan Society for the promotion of Science.
UT Southwestern's Harold C. Simmons Cancer Center is the only National Cancer Institute-designated cancer center in North Texas and one of just 66 NCI-designated cancer centers in the nation. It includes 13 major cancer care programs with a focus on treating the whole patient with innovative treatments, while fostering groundbreaking basic research that has the potential to improve patient care and prevention of cancer worldwide. In addition, the Center's education and training programs support and develop the next generation of cancer researchers and clinicians.
About UT Southwestern Medical Center
UT Southwestern, one of the premier academic medical centers in the nation, integrates pioneering biomedical research with exceptional clinical care and education. The institution's faculty includes many distinguished members, including six who have been awarded Nobel Prizes since 1985. Numbering more than 2,700, the faculty is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide medical care in 40 specialties to nearly 91,000 hospitalized patients and oversee more than 2 million outpatient visits a year.
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