Oct 10, 2006    #153
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Manuscript by School of Dentistry faculty publishes in Nature Genetics Outside-the-box findings expand current, limited understanding of the body’s phosphate regulation

Nature Genetics has published new findings on genetic hypophosphatemia led by investigators from the University of Missouri-Kansas City (UMKC) School of Dentistry. The manuscript is now available on the journal’s Advance Online Publication.

Reviewers of the manuscript refer to the study’s findings as “thinking outside the current dogma,” stimulating new strategies to expand current, limited understanding of phosphate homeostasis.

Acute or chronic low phosphate or elevated phosphate can affect the musculoskeletal, neurological, and cardiovascular systems. This study addresses heritable forms of hypophosphatemia, or low phosphate, which can cause numerous debilitating symptoms, depending on severity.

Genetic or familial hypophosphatemic rickets is relatively rare affecting about 1 in 20,000 people. The first signs in a child are usually bone abnormalities and poorly erupting teeth with rickets, bowing of the legs, bone pain and muscle weakness. As the condition progresses, these individuals are of short stature and suffer with walking and movement due to “soft bones” and can suffer from oral infections due to poorly erupting teeth.

“There were two concepts that were unique and represent thinking ‘outside the box,’ ” UMKC Curators’ Professor Lynda Bonewald, Ph.D., said. “The first was that a protein called Dentin Matrix Protein 1, found mainly in mineralized tissue, could potentially be involved in phosphate metabolism; and the second was that a bone cell called the osteocyte could have a function in phosphate metabolism. Neither of these two concepts had previously been published.”

Bonewald and UMKC School of Dentistry professor Jian Q. Feng, Ph.D., were responsible for laying the groundwork for this study.

Contributing investigators were Shiguang Liu, M.D., Ph.D., and L. Darryl Quarles, M.D., both from the University of Kansas Medical Center; Kenneth White, Ph.D., from the University of Indiana; and Leanne Ward, M.D., from the University of Ottawa in Canada. Investigators from the universities of Wisconsin and McGill in Canada also participated in this study.

Each investigator brought with them different areas of expertise, resulting in novel findings that could lead to means to identify and treat patients before they develop debilitating musculoskeletal symptoms.

The manuscript is titled “Loss of DMP1 causes rickets and osteomalacia and identifies a role for osteocytes in mineral metabolism.”

All monthly Nature Research Journals (Nature Biotechnology, Nature Cell Biology, Nature Genetics, Nature Immunology, Nature Materials, Nature Medicine, Nature Neuroscience and Nature Structural & Molecular Biology) offer Advance Online Publication (AOP) on their websites — the latest research papers, published online ahead of print. These online versions are definitive and may be cited using the digital object identifier.

The UMKC School of Dentistry provides a four-year curriculum that combines classroom education with clinical experience. The school maintains teaching relationships with six hospitals and five community health clinics. It is the only dental school in Missouri and neighboring Kansas. In addition to teaching and service, research is an element vital to the school’s identity and international reputation.

UMKC, one of four University of Missouri campuses, is a public university serving more than 14,000 undergraduate, graduate and professional students. UMKC engages with the community and economy based on a three-part mission: visual and performing arts, health and life sciences, and urban affairs.



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