In our lifetime, many will suffer from diseases that are commonly associated with defective cellular mineralization. These diseases range from osteoporosis, with a reduction in bone and mineral content, to those with an inappropriate increase in mineralization, such as arthritis and atherosclerosis. These diseases certainly involve inappropriate maintenance and maturation of progenitor cells, but may also involve defects in the ultimate function of the cell. Mineralization is a complex process that requires temporal and spatial regulation of specific proteins. The mechanisms by which osteoblastic cells regulate mineralization, the ultimate step in differentiation, are being investigated. Annexin 2 has been identified as an important protein in the regulation of osteoblastic mineralization. Annexin 2 enhances the mineralization capacity of matrix vesicles by increasing, at least in part, the activity of alkaline phosphatase. Annexin 2 has been localized to specialized membrane domains referred to as lipid rafts, where it co-localizes with, and increases the activity of, alkaline phosphatase. Lipid rafts serve as a docking platform for functional units of proteins and when lipid raft integrity is disrupted, mineralization potential is compromised. We propose that lipid rafts serve as platforms for signaling involved in regulating the cellular content and subsequent osteoblastic mineralization. The role of signaling molecules, such as Erk and cPLA2, will be evaluated over the course of osteoblastic mineralization relative to lipid raft integrity. In addition, we hypothesize that the differential activation of Erk during mineralization is secondary to Annexin 2 expression; therefore, the contribution of Annexin 2 to the regulation of these and other signaling molecules will be evaluated. The intracellular mechanisms by which mineralization is controlled are likely conserved, therefore characterization in osteoblasts may provide insight into osteoblast-related diseases such as osteoporosis, but may also contribute to the understanding of inappropriate mineralization in other cell types during disease. ? ? ? ?
| Gillette, Jennifer M; Gibbs, C Parker; Nielsen-Preiss, Sheila M (2008) Establishment and characterization of OS 99-1, a cell line derived from a highly aggressive primary human osteosarcoma. In Vitro Cell Dev Biol Anim 44:87-95 |
