Ion channels in osteoblasts: a story of two intracellular organelles.

Recent advances have highlighted a synchronous coordination of osteoblast and osteoclast activity, whereby, the osteoblast collates all signals applied to the bone and activates osteoclastic resorption. The resorption of the bone and its matrix then releases growth factors held within the matrix (bone morphogenetic proteins, insulin-like growth factors and transforming growth factors) which then stimulate the osteoblast to lay down new osteoid. In healthy adults there is a balance between bone deposition and bone loss and there is no net gain or loss, and the amount of calcium (Ca2+) ingested in the diet is equal to that which is excreted. In the early stages of life, the emphasis is on bone building and more Ca2+ is retained from the diet and more bone deposited as the skeleton matures. As we age, and, in particular in postmenopausal women, the osteoclastic activity outweighs the bone deposition and the patient loses bone becoming osteoporotic. The focus of the work reported here was to identify and dissect the various cytosolic intracellular signalling pathways within osteoblasts and establish the importance of each under different physiological conditions. In brief, two basic signalling pathways exist; one is linked with a seven transmembrane spanning protein and specific receptors for ligands (the G protein linked pathways) and one pathway is linked with protein phosphorylation especially of the tyrosine kinases. In general, G protein activity is associated with endocrine ligands such as parathyroid hormone (PTH) and (calcitonin has been linked with tyrosine kinase activity) tyrosine kinase activity is linked with adhesion of osteoblasts and recognition of the substrate to which they are attached. Our specific areas of interest are the ways in which Ca2+ activity within the cell is modified and used as a signal for further activation and possibly differential gene activation.