The project described in this proposal is aimed at characterizing the role of the mannose receptor in osteoblasts. The functional domains of the receptor relevant to bone cell activity will be determined as well as the mechanism of signal transduction. Lastly, the potential for disruption of receptor function in inflammatory mediated bone loss will be investigated. This last aim addresses the potential mechanism by which alveolar bone may be compromised in periodontal disease. Specifically, we will i) prove that the mannose receptor is preferentially expressed during osteoblast maturation, ii) create stably transfected cell lines expressing fragments of the receptor for analysis of the carbohydrate recognition domains in osteoblasts, iii) show that calcium transients and the IP3/DAG pathways are involved in cell signalling and lastly, iv) demonstrate that glycosidases can destroy specific oligosaccharide structures that bind to (and activate) osteoblasts. We speculate that this last point is the reason for the haphazard and inappropriate degree of bone formation that exists in periodontally affected alveolar bone.
| Reynolds, S D; Zhang, D; Puzas, J E et al. (2000) Cloning of the chick BMP1/Tolloid cDNA and expression in skeletal tissues. Gene 248:233-43 |
| Landesberg, R; Takeuchi, E; Puzas, J E (1999) Differential activation by cytokines of mitogen-activated protein kinases in bovine temporomandibular-joint disc cells. Arch Oral Biol 44:41-8 |
