Department of Joint and Trauma Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
Department of Plastic Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
FEBS Open Bio. 2020 Nov;10(11):2478-2488. doi: 10.1002/2211-5463.12974. Epub 2020 Oct 25.
Joint contracture (also known as arthrofibrosis) is a fibrotic joint disorder characterized by excessive collagen production to form fibrotic scar tissue and adhesions within joint capsules. This can severely affect day-to-day activities and quality of life because of a restricted range of motion in affected joints. The precise pathogenic mechanism underlying joint contractures is not fully understood. Lumican belongs to the class II small leucine-rich repeat proteoglycan superfamily, which makes up collagen fibrils in the extracellular matrix. Lumican is ubiquitously expressed in the skin, liver, heart, uterus and articular cartilage and has reported roles in cell migration, proliferation, angiogenesis and Toll-like receptor 4 signaling. Previous research has suggested that lumican is involved in the pathogenesis of several fibrotic diseases. Because joint contracture resembles a fibrotic disease, we aimed to investigate the role of lumican in the development of joint contracture in vitro. Here, we showed that protein levels were up-regulated in the fibrotic joint capsule versus control. We observed that lumican significantly enhanced the proliferation, migration and fibroblast-myofibroblast transition of synovial fibroblasts. Moreover, lumican led to increased transcription of alpha-smooth muscle actin, matrix metallopeptidase 9, Collagen I, plasminogen activator inhibitor 1 and transforming growth factor-β in vitro. Lumican treatment promoted collagen lattice contraction in a dose-dependent manner as early as 24 h after treatment. Thus, our studies reveal that lumican could promote fibroblast-myofibroblast transition and joint contracture.
关节挛缩（也称为关节纤维化）是一种纤维性关节疾病，其特征是胶原过度产生，在关节囊内形成纤维性瘢痕组织和粘连。由于受影响关节的活动范围受限，这会严重影响日常活动和生活质量。关节挛缩的确切发病机制尚不完全清楚。赖氨酰聚糖（Lumican）属于 II 类富含亮氨酸的小纤维蛋白聚糖超家族，构成细胞外基质中的胶原纤维。赖氨酰聚糖在皮肤、肝脏、心脏、子宫和关节软骨中广泛表达，据报道在细胞迁移、增殖、血管生成和 Toll 样受体 4 信号转导中发挥作用。先前的研究表明，赖氨酰聚糖参与了几种纤维性疾病的发病机制。由于关节挛缩类似于纤维性疾病，我们旨在研究赖氨酰聚糖在关节挛缩发病机制中的作用。在这里，我们发现纤维化关节囊中赖氨酰聚糖蛋白水平上调。我们观察到赖氨酰聚糖显著增强了滑膜成纤维细胞的增殖、迁移和纤维母细胞-肌成纤维细胞转化。此外，赖氨酰聚糖导致体外α-平滑肌肌动蛋白、基质金属蛋白酶 9、胶原 I、纤溶酶原激活物抑制剂 1 和转化生长因子-β的转录增加。赖氨酰聚糖处理以剂量依赖性方式促进胶原晶格收缩，早在处理后 24 小时即可观察到。因此，我们的研究表明，赖氨酰聚糖可促进成纤维细胞-肌成纤维细胞转化和关节挛缩。
