Kobayashi Takashi, Kakizaki Ikuko, Nozaka Hiroyuki, Nakamura Toshiya
Department of Glycotechnology, Center for Advanced Medical Research, Graduate School of Medicine, Hirosaki University, 5 Zaifu-cho, Hirosaki, Aomori 036-8562, Japan.
Departments of Bioscience and Laboratory Medicine, Hirosaki University Graduate School of Health Sciences, 66-1 Hon-cho, Hirosaki, Aomori 036-8564, Japan.
Biochem Biophys Rep. 2016 Nov 18;9:72-78. doi: 10.1016/j.bbrep.2016.11.009. eCollection 2017 Mar.
Because cartilage lacks nerves, blood vessels, and lymphatic vessels, it is thought to contain factors that inhibit the growth and development of those tissues. Chondroitin sulfate proteoglycans (CSPGs) are a major extracellular component in cartilage. CSPGs contribute to joint flexibility and regulate extracellular signaling their attached glycosaminoglycan, chondroitin sulfate (CS). CS and CSPG inhibit axonal regeneration; however, their role in blood vessel formation is largely unknown. To clarify the function of CSPG in blood vessel formation, we tested salmon nasal cartilage proteoglycan (PG), a member of the aggrecan family of CSPG, for endothelial capillary-like tube formation. Treatment with salmon PG inhibited endothelial cell adhesion and tube formation. The anti-angiogenic activity was derived from CS in the salmon PG but not the core protein. Salmon PG also reduced matrix metalloproteinase expression and inhibited angiogenesis in the chick chorioallantoic membrane. All of these data support an anti-angiogenic role for CSPG in cartilage.
由于软骨缺乏神经、血管和淋巴管,因此人们认为它含有抑制这些组织生长和发育的因子。硫酸软骨素蛋白聚糖(CSPG)是软骨中的主要细胞外成分。CSPG通过其附着的糖胺聚糖硫酸软骨素(CS)促进关节灵活性并调节细胞外信号传导。CS和CSPG抑制轴突再生;然而,它们在血管形成中的作用很大程度上未知。为了阐明CSPG在血管形成中的功能,我们测试了鲑鱼鼻软骨蛋白聚糖(PG),它是CSPG聚集蛋白聚糖家族的成员,对内皮细胞毛细血管样管形成的影响。用鲑鱼PG处理可抑制内皮细胞黏附和管形成。抗血管生成活性源自鲑鱼PG中的CS而非核心蛋白。鲑鱼PG还降低了基质金属蛋白酶的表达并抑制了鸡胚绒毛尿囊膜中的血管生成。所有这些数据都支持CSPG在软骨中具有抗血管生成作用。