In contrast to what is known about the effects of lead on the developing growth plate, its effect on the adult skeleton is subtle. This is most probably due to the slower turnover of mature bone. However, a number of animal studies and preliminary human data indicate that lead exposure may ultimately compromise skeletal mass in the elderly. This proposal seeks to investigate the cellular mechanisms for this pathology. The investigators have developed an in vitro cell model that faithfully resembles the remodeling process of osteoclastic bone resorption followed by osteoblastic bone formation. With this model they can investigate the influence of lead on the communication between these cells. Moreover, they can also determine if lead in the medium (i.e. extracellular fluid) or in the matrix (i.e. in the bone) has different effects on osteoclasts and osteoblasts. The assays the PI will use to make these measurements include pit formation on devitalized bone by osteoclasts, immunocytochemical analyses, cell proliferation assays and biochemical determinants for bone formation. The investigator will also investigate the mechanisms of lead's interference with second messenger signals (i.e. intracellular calcium concentrations and transients) in these cells. Lastly, the effect of lead on the synthesis of growth factors by osteoblasts will be investigated. The results of these experiments will provide the cellular basis for a better understanding of the toxic effects of this ion.
| Sheu, Tzong-Jen; Schwarz, Edward M; Martinez, Daniel A et al. (2003) A phage display technique identifies a novel regulator of cell differentiation. J Biol Chem 278:438-43 |
| Boyan, B D; Schwartz, Z; Lohmann, C H et al. (2003) Pretreatment of bone with osteoclasts affects phenotypic expression of osteoblast-like cells. J Orthop Res 21:638-47 |
| Zuscik, Michael J; Pateder, Dhruv B; Puzas, J Edward et al. (2002) Lead alters parathyroid hormone-related peptide and transforming growth factor-beta1 effects and AP-1 and NF-kappaB signaling in chondrocytes. J Orthop Res 20:811-8 |
| Sheu, Tzong-Jen; Schwarz, Edward M; O'Keefe, Regis J et al. (2002) Use of a phage display technique to identify potential osteoblast binding sites within osteoclast lacunae. J Bone Miner Res 17:915-22 |
