2004 WHRG Grant Program

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IP₆ Inhibits Osteoporosis by Down-Regulating Matrix Metalloproteinases
Ivana Vucenik, Ph.D.
School of Medicine, University of Maryland, Baltimore

Osteopororsis is a skeletal disease characterized by low bone mass and deterioration of bone tissue. Diseases of the bone, in particular osteoporosis, represent a major healthcare problem, affecting approximately one-half of all women and one-fourth of all men over age 50. Since rate of osteoporotic fractures are low in Oriental populations who eat more cereal and legume-based diets (rice, soybean and soy products contain high inosital hexaphosphate-IP₆), a natural question is: is IP₆ protective against skeletal diseases? If so, will IP₆ and diets containing high IP₆ be effective in preventing and treating osteoporosis?

This novel feature of IP₆ has never been investigated, and no published data on the effect of IP₆ on osteoporosis exist. Encouraged by preliminary data, here we propose the following aims:

Aim 1: To identify the effect of IP₆ on bone cells of osteoblastic and osteoclastic lineages.
Hypothesis: IP₆ enhances osteoblast-like cell proliferation and function, and inhibits the recruitment and function of osteoclasts.
Approach: Proliferation, growth, and differentiation of osteoblast and osteoclast cell cultures in vitro will be studied.

Aim 2: To study the effect of IP₆ on the expression and activity of matrix metalloproteinases (MMPs).
Hypothesis: IP₆ prevents osteoporosis by inhibiting and down-regulating MMPs.
Approach: The effect of IP₆ on activity and expression of MMPs will be evaluated in vitro by zymography and ELISA to examine the mechanism by which IP₆ acts on bone.

In a search for alternative "natural" therapies, the data from these initial studies would be helpful in designing strategies for prevention and treatment of osteoporosis by IP₆ in animal models and in humans.

Because of the novelty of the proposal, there is urgency to generate preliminary data that will render the proposal competitive for extramural funding. Since IP₆ holds promise as a novel and natural therapeutics for prevention of osteoporosis and other human disease associated with bone loss, we seek support from the Women's Health Research Group to perform "pioneering" critical studies, since it is likely that this project has a potential to attract future funding from different sources.