Molecular Targets for Anabolic Bone Therapies

DESCRIPTION (provided by applicant): Current literature on the gene expression evaluation of mammalian or human osteoblasts is scant, particularly studies of primary human cells as opposed to animal or cell line investigations. We hypothesize that analysis of gene expression profiles from individual osteogenic growth factors will result in novel gene/ protein networks for each osteogenic growth factors tested. Further, these networks may interact with canonical pathways in new or unique ways, as well as novel intracellular gene/protein networks. Importantly, analysis of both of these may provide new molecular targets for anabolic bone therapies. We further postulate that the analysis of composite cellular gene/protein networks (referred to herein as "super- networks"), constructed from individual osteogenic growth-factor specific networks, will yield common mechanisms important to the processes of bone formation. Velcura Therapeutics, Inc. has pioneered the use of primary human bone cells (preosteoblasts) as targets in novel ex vivo bone formation assays designed to develop therapies that stimulate bone formation for the treatment of bone diseases such as osteoporosis. The intent of this Phase I SBIR is to establish the presence of novel and/or common cellular gene/protein networks, validate their existence, and determine a rank-order of molecular targets for the identification of anabolic bone therapies. Thus, the goals of this SBIR are to determine whether: (1) novel aspects of osteoblast intracellular gene/protein networks can be identified and validated, (2) there are the common intercellular networks utilized during bone formation, and (3) what are the important molecular targets for this process