Articular cartilage is considered to have limited regenerative capacity, which has led to the search for therapies to limit or halt the progression of its destruction. Perlecan, a multifunctional heparan sulphate (HS) proteoglycan, promotes embryonic cartilage development and stabilises the mature tissue. We investigated the immunolocalisation of perlecan and collagen between donor-matched biopsies of human articular cartilage defects (n = 10 × 2) that were repaired either naturally or using autologous cell therapy, and with age-matched normal cartilage. We explored how the removal of HS from perlecan affects human chondrocytes in vitro. Immunohistochemistry showed both a pericellular and diffuse matrix staining pattern for perlecan in both natural and cell therapy repaired cartilage, which related to whether the morphology of the newly formed tissue was hyaline cartilage or fibrocartilage. Immunostaining for perlecan was significantly greater in both these repair tissues compared to normal age-matched controls. The immunolocalisation of collagens type III and VI was also dependent on tissue morphology. Heparanase treatment of chondrocytes in vitro resulted in significantly increased proliferation, while the expression of key chondrogenic surface and genetic markers was unaffected. Perlecan was more prominent in chondrocyte clusters than in individual cells after heparanase treatment. Heparanase treatment could be a means of increasing chondrocyte responsiveness to cartilage injury and perhaps to improve repair of defects.

中文翻译：

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Perlecan在人类成年软骨的自然和细胞疗法修复中：这种蛋白聚糖的修饰可以成为一种新颖的治疗方法吗？

关节软骨被认为具有有限的再生能力，这导致寻求限制或阻止其破坏进展的疗法。Perlecan是一种多功能硫酸乙酰肝素（HS）蛋白聚糖，可促进胚胎软骨发育并稳定成熟组织。我们研究的基底膜蛋白聚糖的人关节软骨缺损的供体匹配的活检（之间的免疫定位和胶原Ñ= 10×2），可以自然修复或使用自体细胞疗法修复，并具有与年龄匹配的正常软骨。我们探索了如何从全白细胞胶中去除HS对体外人软骨细胞的影响。免疫组织化学显示在自然和细胞疗法修复的软骨中，Perlecan的细胞周围和弥漫性基质染色模式都与新形成的组织的形态是透明软骨还是纤维软骨有关。与正常年龄匹配的对照组相比，在这两种修复组织中对perlecan的免疫染色明显更高。III型和VI型胶原蛋白的免疫定位也取决于组织形态。肝素酶体外处理软骨细胞导致增殖明显增加，而关键软骨形成表面和遗传标记的表达不受影响。乙酰肝素酶处理后，Perlecan在软骨细胞簇中比在单个细胞中更为突出。乙酰肝素酶治疗可能是增加软骨细胞对软骨损伤反应性的一种手段，并且可能是改善缺陷修复的一种手段。