Dodds Robert A
Growth Factors Drug Discovery, Johnson and Johnson Pharmaceutical Research and Development, Raritan, NJ 08869, USA.
Cell Biochem Funct. 2003 Sep;21(3):231-4. doi: 10.1002/cbf.1078.
Cathepsin K is a member of the papain superfamily of cysteine proteases and plays a pivotal role in osteoclast-mediated bone resorption. This enzyme is an excellent target for antiresorptive therapies for osteopenic disorders such as osteoporosis.(1) Although isolated inhibitor studies on purified enzymes is required to discover potent and selective inhibitors of cathepsin K, a quantitative cytochemical assay(2) for cathepsin K would allow inhibitors to be tested on actual osteoclasts within sections of bone. Furthermore cathepsin K activity could be used to identify and analyse osteoclasts at definitive stages of their lifespan. A cytochemical assay is described that localizes osteoclast cathepsin K activity in unfixed, undecalcified cryostat sections of animal and human bone.
组织蛋白酶K是半胱氨酸蛋白酶木瓜蛋白酶超家族的成员,在破骨细胞介导的骨吸收中起关键作用。这种酶是骨质疏松症等骨质减少性疾病抗吸收治疗的理想靶点。(1)虽然需要对纯化的酶进行单独的抑制剂研究以发现有效的组织蛋白酶K选择性抑制剂,但一种针对组织蛋白酶K的定量细胞化学分析方法(2)将使抑制剂能够在骨切片中的实际破骨细胞上进行测试。此外,组织蛋白酶K活性可用于识别和分析破骨细胞生命周期特定阶段的细胞。本文描述了一种细胞化学分析方法,该方法可在动物和人类骨骼的未固定、未脱钙低温恒温切片中定位破骨细胞组织蛋白酶K的活性。