Grant: Operating Grant

Osteoporosis, the most prevalent metabolic bone disease, affects the elderly. Daily subcutaneous injection ('intermittent treatment') with human parathyroid hormone (PTH) (Teriparatide or Fortéo®) is the only approved treatment for increasing bone mass in osteoporosis patients. The mechanisms involved in the bone-forming effects of intermittent PTH treatment are not fully understood. Our research is aimed at studying those mechanisms in order to identify new targets for the development of therapeutics for osteoporosis. We have found that when PTH binds its receptor in bone cells, it activates signals that send the protein alphaNAC to the nucleus of the cells. In turn, the nuclear alphaNAC protein regulates the expression of other genes. We believe that this 'pathway', i.e. the transmission of signals from PTH and its receptor, through alphaNAC, to the nucleus of the cell to affect gene expression is important for the bone-forming action of PTH. We propose to use several state-of-the-art techniques in cellular biology, molecular biology, and molecular genetics to confirm that the PTH signals that send alphaNAC to the nucleus mediate the bone-forming action of PTH. Once we establish the type and sequence of signals and when the mechanisms are further known, this research will provide the foundation for the development of new drugs for osteoporosis.