Bone and Cartilage Research Unit, Arthropôle Liège, University of Liège, Liège, Belgium.
Orthopedic Department, Cliniques Universitaires Saint-Luc, Brussels, Belgium.
Cartilage. 2021 Dec;13(2_suppl):862S-871S. doi: 10.1177/1947603519870855. Epub 2019 Aug 27.
Syndecan-4 plays a critical role in cartilage degradation during osteoarthritis (OA). The aim of this study was to investigate the expression and localization of syndecan-4 in different OA joint tissues.
Syndecan-4 mRNA levels were quantified by reverse transcription-polymerase chain reaction in human OA primary cells. Syndecan-4 was localized by immunohistochemistry in knee, hip, or shoulder OA bone/cartilage biopsies. Syndecan-4 was quantified by immunoassay in chondrocytes culture supernatant and cell fraction.
Using immunochemistry, syndecan-4 was observed in chondrocytes clusters in the superficial zone of OA knee, but not in OA hip or shoulder cartilage. No significant difference was detected in syndecan-4 expression level in sclerotic compared with nonsclerotic osteoblasts or in inflamed synoviocytes compared to normal/reactive ones. Differentiated hypertrophic chondrocytes from knee, but not from hip cartilage, expressed more syndecan-4 than nonhypertrophic cells. Using an immunoassay for the extracellular domain of syndecan-4, we found 68% of the syndecan-4 in the culture supernatant of OA chondrocytes culture, suggesting that a large majority of the syndecan-4 is shed and released in the extracellular medium. The shedding rate was not affected by hypertrophic differentiation state of the chondrocytes or their joint origin.
Even if chondrocytes clusters are seen in OA knee, hip and shoulder cartilage and hypertrophic differentiation appears in knee and hip OA articular chondrocytes, syndecan-4 synthesis only increased in knee. These findings suggest the presence of biochemical difference between articular cartilage according to their location and that syndecan-4 could be a biochemical marker specific for knee OA.
在骨关节炎（OA）中，硫酸乙酰肝素蛋白聚糖-4（Syndecan-4）在软骨降解中发挥关键作用。本研究旨在探讨不同 OA 关节组织中 Syndecan-4 的表达和定位。
通过逆转录-聚合酶链反应（RT-PCR）定量检测人 OA 原代细胞中 Syndecan-4 mRNA 水平。通过免疫组织化学法检测膝、髋或肩 OA 骨/软骨活检中 Syndecan-4 的定位。通过免疫测定法检测软骨细胞培养上清液和细胞级分中的 Syndecan-4。
免疫化学法显示，OA 膝关节的浅层软骨细胞簇中有 Syndecan-4，而 OA 髋关节或肩关节软骨中则没有。硬化性骨细胞中 Syndecan-4 的表达水平与非硬化性骨细胞相比，或炎症性滑膜细胞与正常/反应性滑膜细胞相比，无显著差异。与非肥大细胞相比，来自膝部而非髋部软骨的分化为肥大的软骨细胞表达更多的 Syndecan-4。使用 Syndecan-4 细胞外结构域的免疫测定法，我们发现 OA 软骨细胞培养上清液中有 68%的 Syndecan-4，提示大部分 Syndecan-4 被脱落并释放到细胞外基质中。软骨细胞的肥大分化状态或其关节来源并不影响脱落率。
尽管 OA 膝关节、髋关节和肩关节软骨中可见软骨细胞簇，且膝部和髋部 OA 关节软骨中的软骨细胞出现肥大分化，但只有膝部的 Syndecan-4 合成增加。这些发现表明，根据其位置，关节软骨存在生化差异，并且 Syndecan-4 可能是膝骨关节炎的生化标志物。
