Perlecan in the Natural and Cell Therapy Repair of Human Adult Articular Cartilage: Can Modifications in This Proteoglycan Be a Novel Therapeutic Approach?
Perlecan in the Natural and Cell Therapy Repair of Human Adult Articular Cartilage: Can Modifications in This Proteoglycan Be a Novel Therapeutic Approach?
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串珠素在成人关节软骨天然和细胞治疗修复中的作用：这种蛋白聚糖的修饰能成为一种新的治疗方法吗？
DOI：
10.3390/biom11010092
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发表时间：
2021-01-13
期刊：
影响因子：
5.5
通讯作者：
Roberts S
中科院分区：
文献类型：
--
作者：
Garcia J;McCarthy HS;Kuiper JH;Melrose J;Roberts S
关节软骨被认为具有有限的再生能力，这促使人们寻找限制或停止其破坏进程的治疗方法。Perlecan是一种多功能硫酸肝素（HS）蛋白多糖，促进胚胎软骨发育并稳定成熟组织。我们研究了自然修复或使用自体细胞疗法修复的人类关节软骨缺损（n = 10 × 2）的供体匹配活检与年龄匹配的正常软骨之间的perlecan和胶原的免疫定位。我们探讨了从perlecan中去除HS对体外人软骨细胞的影响。免疫组化结果显示，自然修复和细胞治疗修复的软骨中，perlecan均呈细胞周和弥漫性基质染色模式，这与新形成的组织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，这两种修复组织中perlecan的免疫染色明显更大。III型和VI型胶原的免疫定位也依赖于组织形态。肝素酶处理的软骨细胞体外增殖显著增加，而关键软骨表面和遗传标记的表达不受影响。肝素酶治疗后，Perlecan在软骨细胞团中比在单个细胞中更为突出。肝素酶治疗可能是一种增加软骨细胞对软骨损伤的反应性的方法，也许可以改善软骨缺损的修复。
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.
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影响因子：
2.7
作者：
Gomes, RR;Farach-Carson, MC;Carson, DD
通讯作者：
Carson, DD
影响因子：
7
作者：
Loeser, RF;Sadiev, S;Goldring, MB
通讯作者：
Goldring, MB
影响因子：
6
作者：
Huegel, Julianne;Enomoto-Iwamoto, Motomi;Pacifici, Maurizio
通讯作者：
Pacifici, Maurizio
影响因子：
11
作者：
Cheng CC;Lee YH;Lin SP;Huangfu WC;Liu IH
通讯作者：
Liu IH
影响因子：
3.1
作者：
Hayes, A. J.;Shu, C. C.;Melrose, J.
通讯作者：
Melrose, J.