KLK4调控骨微环境稳态并介导骨巨细胞瘤溶骨破坏的机制研究

Giant cell tumor of bone is a malignant bone tumor characterized by osteolytic destruction. The pain caused by bone destruction and pathological fracture are the important reasons behind the decline in patients' quality of life. We used a large number of clinical samples and found an abnormally high expression of a kallikrein KLK4 associated with bone metabolism in giant cell tumor of bone. Using transgenic technology, we discovered an increase in the bone density of KLK4 knockout mice and trabecular number. Further study found that KLK4 catalyzes the hydrolysis of bone matrix protein IGF-II and thrombin receptor 1, and may be used to mediate the regulation of bone metabolism. The team planned to start with a large number of clinical samples to clarify the correlation between KLK4 and the occurrence and destruction of giant cell tumor of bone. We also aimed to elucidate the role of KLK4 in the proliferation, angiogenesis and bone microenvironment balance of giant cell tumor of bone at the molecular, cellular and in vivo levels, in order to provide a new theoretical basis and drug targets for basic research and clinical treatment.

骨巨细胞瘤是一种以溶骨性破坏为特点的交界恶性骨肿瘤，骨破坏导致的疼痛及病理性骨折是导致患者生存质量下降的重要原因。我们利用大量的临床样本明确了一种与骨代谢相关的激肽释放酶KLK4在骨巨细胞瘤中存在异常的高表达；利用转基因技术我们发现KLK4敲除鼠骨密度及骨小梁数量有明显提高；进一步研究发现 KLK4催化骨基质成份蛋白IGF-II及凝血酶受体1的水解，并可能以此介导骨代谢的调控。项目组拟从大量临床样本入手，明确KLK4与骨巨细胞瘤发生及骨破坏的相关性；在分子、细胞及在体水平阐明KLK4在骨巨细胞瘤增殖，血管生成，及骨微环境平衡中的作用，为骨巨细胞瘤基础及临床研究提供新的理论依据及药物靶点。

骨巨细胞瘤是一种以溶骨性破坏为特点的交界恶性骨肿瘤，骨破坏导致的疼痛及病理性骨折是导致患者生存质量下降的重要原因。我们利用大量的临床样本明确了一种与骨代谢相关的激肽释放酶KLK4在骨巨细胞瘤中存在异常的高表达；利用转基因技术我们发现KLK4敲除鼠骨密度及骨小梁数量有明显提高；进一步研究发现 KLK4催化骨基质成份蛋白IGF-II及凝血酶受体1的水解，并可能以此介导骨代谢的调控。本项目通过大量临床样本入手，明确KLK4与骨巨细胞瘤发生及骨破坏的相关性；在分子、细胞及在体水平阐明KLK4在骨巨细胞瘤增殖，血管生成，及骨微环境平衡中的作用，为骨巨细胞瘤基础及临床研究提供新的理论依据及药物靶点。