The Role of P62/A170 in Pathological Bone Destruction

P62/A170 在病理性骨破坏中的作用

• 批准号: nhmrc : 353673
• 负责人: Dr Lin Huang
• 金额: $ 18.4万
• 依托单位: The University of Western Australia
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2005
• 资助国家: 澳大利亚
• 起止时间: 2005-01-01 至 2007-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/role-p62a170-pathological-bone-destruction/94831
• 关键词: Role; P62; A170; Pathological; Bone

Approximately up to 30% of patients are admitted to public hospitals in Australia for reasons related to skeletal disorders, including trauma, osteoarthritis, osteoporosis, primary and secondary bone tumours, genetic and metabolic disorders. Abnormal bone resorption contributes to most of these diseases and conditions. Based on the clinical evidence of P62 mutation in patients with Paget's Disease of bone and our observation of the involvement of P62 in RANKL-induced NF-Kb signaling, we propose that intracellular molecule P62-A172 may play an important part in the switch off-on signals necessary for bone resorbing cells to resorb bone. To this end, we will study the molecular mechanism of P62 in action, and the interaction with its possible partners for the facilitation of abnormal bone resorption. The clinical significance of this project is to: 1) enhance understanding of abnormal bone resorption in Orthopaedic related diseases and conditions. 2) provide a strategy of drug development for the treatment of these disease and conditions.

在澳大利亚，大约有高达 30% 的患者因与骨骼疾病相关的原因而被送往公立医院，这些疾病包括创伤、骨关节炎、骨质疏松症、原发性和继发性骨肿瘤、遗传和代谢紊乱。骨吸收异常是大多数这些疾病和病症的原因。基于佩吉特骨病患者 P62 突变的临床证据以及我们对 P62 参与 RANKL 诱导的 NF-Kb 信号传导的观察，我们提出细胞内分子 P62-A172 可能在骨吸收细胞吸收骨所需的开关信号中发挥重要作用。为此，我们将研究 P62 作用的分子机制，以及与其可能的伙伴相互作用以促进异常骨吸收。该项目的临床意义在于：1）增强对骨科相关疾病和病症中骨吸收异常的认识。 2) 提供治疗这些疾病和病症的药物开发策略。