CARBOHYDRATE RECOGNITION DOMAINS ON OSTEOBLASTS

成骨细胞上的碳水化合物识别域

• 批准号: 2414696
• 负责人: J. Edward PUZAS
• 金额: $ 23.15万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-05-01 至 2000-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2414696
• 关键词: affinity chromatography; biological signal transduction; bone development; calcium flux; carbohydrate structure; dental alveolus; diacylglycerols; glycosidases; immunocytochemistry; inflammation; inositol phosphates; laboratory rat; mannose; northern blottings; oligosaccharides; osteoblasts; osteocytes; osteoporosis; periodontitis; protein kinase C; receptor expression; second messengers; tissue /cell culture; western blottings

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.

本提案中描述的项目旨在描述角色 成骨细胞中的甘露糖受体。的功能域 将确定与骨细胞活性相关的受体以及 信号转导机制。最后，破坏的可能性 将研究炎症介导的骨质流失中的受体功能。 最后一个目标解决了牙槽骨可能的潜在机制 受到牙周病的影响。 具体来说，我们将 i) 证明甘露糖受体优先 在成骨细胞成熟期间表达，ii) 创建稳定转染的细胞 表达受体片段的细胞系，用于分析 成骨细胞中的碳水化合物识别域，iii) 表明钙 瞬态和 IP3/DAG 通路参与细胞信号传导和 最后，iv）证明糖苷酶可以破坏特定的 结合（并激活）成骨细胞的寡糖结构。我们 推测最后一点是偶然的原因 牙周内存在不适当的骨形成程度 受影响的牙槽骨。