McCulloch Daniel R, Le Goff Carine, Bhatt Sumantha, Dixon Laura J, Sandy John D, Apte Suneel S
Department of Biomedical Engineering and Orthopaedic and Rheumatologic Institute, ND20-Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
Gene Expr Patterns. 2009 Jun;9(5):314-23. doi: 10.1016/j.gep.2009.02.006. Epub 2009 Feb 27.
The secreted metalloprotease ADAMTS5 is implicated in destruction of the cartilage proteoglycan aggrecan in arthritis, but its physiological functions are unknown. Its expression profile during embryogenesis and in adult tissues is therefore of considerable interest. beta-Galactosidase (beta-gal) histochemistry, enabled by a LacZ cassette inserted in the Adamts5 locus, and validated by in situ hybridization with an Adamts5 cRNA probe and ADAMTS5 immunohistochemistry, was used to profile Adamts5 expression during mouse embryogenesis and in adult mouse tissues. Embryonic expression was scarce prior to 11.5 days of gestation (E11.5) and noted only in the floor plate of the developing brain at E 9.5. After E11.5 there was continued expression in brain, especially in the choroid plexus, peripheral nerves, dorsal root ganglia, cranial nerve ganglia, spinal and cranial nerves, and neural plexuses of the gut. In addition to nerves, developing limbs have Adamts5 expression in skeletal muscle (from E13.5), tendons (from E16.5), and inter-digital mesenchyme of the developing autopod (E13.5-15.5). In adult tissues, there is constitutive Adamts5 expression in arterial smooth muscle cells, mesothelium lining the peritoneal, pericardial and pleural cavities, smooth muscle cells in bronchi and pancreatic ducts, glomerular mesangial cells in the kidney, dorsal root ganglia, and in Schwann cells of the peripheral and autonomic nervous system. Expression of Adamts5 during neuromuscular development and in smooth muscle cells coincides with the broadly distributed proteoglycan versican, an ADAMTS5 substrate. These observations suggest the major contexts in which developmental and physiological roles could be sought for this protease.
分泌型金属蛋白酶ADAMTS5与关节炎中软骨蛋白聚糖聚集蛋白聚糖的破坏有关,但其生理功能尚不清楚。因此,它在胚胎发育过程和成年组织中的表达谱备受关注。通过插入Adamts5基因座的LacZ盒实现的β-半乳糖苷酶(β-gal)组织化学,并通过与Adamts5 cRNA探针的原位杂交和ADAMTS5免疫组织化学进行验证,用于分析小鼠胚胎发育过程和成年小鼠组织中Adamts5的表达。胚胎期在妊娠11.5天(E11.5)之前表达稀少,仅在E9.5时在发育中的脑底板中观察到。E11.5之后,在脑中持续表达,特别是在脉络丛、外周神经、背根神经节、脑神经节、脊髓和脑神经以及肠道神经丛中。除神经外,发育中的肢体在骨骼肌(从E13.5开始)、肌腱(从E16.5开始)和发育中的足端部指间间充质(E13.5 - 15.5)中有Adamts5表达。在成年组织中,动脉平滑肌细胞、腹膜、心包和胸膜腔的间皮、支气管和胰管中的平滑肌细胞、肾脏中的肾小球系膜细胞、背根神经节以及外周和自主神经系统的雪旺细胞中存在组成型Adamts5表达。Adamts5在神经肌肉发育过程和平滑肌细胞中的表达与广泛分布的蛋白聚糖多功能蛋白聚糖(一种ADAMTS5底物)一致。这些观察结果提示了可寻找该蛋白酶发育和生理作用的主要背景。