Medical Education Development Center, Gifu University School of Medicine, 1-1 Yanagido, Gifu City, Gifu 501-1194, Japan.
Research & Development Dept., Ichimaru Pharcos Co., Ltd., 318-1 Asagi, Motosu City, Gifu 501-0475, Japan.
Int J Mol Sci. 2020 Oct 19;21(20):7744. doi: 10.3390/ijms21207744.
Osteoarthritis (OA), a disease that greatly impacts quality of life, has increasing worldwide prevalence as the population ages. However, its pathogenic mechanisms have not been fully elucidated and current therapeutic treatment strategies are inadequate. In recent years, abnormal endochondral ossification in articular cartilage has received attention as a pathophysiological mechanism in OA. Cartilage is composed of abundant extracellular matrix components, which are involved in tissue maintenance and regeneration, but how these factors affect endochondral ossification is not clear. Here, we show that the application of aggrecan-type proteoglycan from salmon nasal cartilage (sPG) exhibited marked proliferative capacity through receptor tyrosine kinases in chondroprogenitor cells, and also exhibited differentiation and three-dimensional structure formation via phosphorylation of Insulin-like Growth Factor-1 Receptor and Growth Differentiation Factor 5 expression. Furthermore, sPG inhibited calcification via expression of Runx2 and Col10 (factors related to induction of calcification), while increasing Mgp, a mineralization inhibitory factor. As a result of analyzing the localization of sPG applied to the cells, it was localized on the surface of the cell membrane. In this study, we found that sPG, as a biomaterial, could regulate cell proliferation, differentiation and calcification inhibition by acting on the cell surface microenvironment. Therefore, sPG may be the foundation for a novel therapeutic approach for cartilage maintenance and for improved symptoms in OA.
骨关节炎（OA）是一种严重影响生活质量的疾病，随着人口老龄化，其在全球的患病率不断增加。然而，其发病机制尚未完全阐明，目前的治疗策略也不够充分。近年来，关节软骨中异常的软骨内骨化已成为 OA 的一种病理生理机制。软骨由丰富的细胞外基质成分组成，这些成分参与组织的维持和再生，但这些因素如何影响软骨内骨化尚不清楚。在这里，我们发现鲑鱼鼻软骨的聚集蛋白聚糖（sPG）通过软骨祖细胞中的受体酪氨酸激酶表现出明显的增殖能力，并且还通过胰岛素样生长因子-1 受体和生长分化因子 5 的表达表现出分化和三维结构形成。此外，sPG 通过表达 Runt 相关转录因子 2 和 Col10（与诱导钙化相关的因子）抑制钙化，同时增加矿化抑制因子 Mgp。通过分析应用于细胞的 sPG 的定位，发现其定位于细胞膜表面。在这项研究中，我们发现 sPG 作为一种生物材料，通过作用于细胞表面微环境，可调节细胞增殖、分化和抑制钙化。因此，sPG 可能为软骨维持和改善 OA 症状的新型治疗方法奠定了基础。
