Department of Human Genetics, Amsterdam UMC Location Vrije Universiteit Amsterdam, Amsterdam, Netherlands.
Department of Clinical Chemistry, Amsterdam UMC Location Vrije Universiteit Amsterdam, Amsterdam, Netherlands.
Front Endocrinol (Lausanne). 2023 Jul 7;14:1168306. doi: 10.3389/fendo.2023.1168306. eCollection 2023.
Since our discovery in 2013 that genetic defects in lead to bone fragility, the mechanistic details of this process have remained obscure. It has been established that variants cause syndromic and nonsyndromic osteoporosis as well as osteoarthritis. PLS3 codes for an actin-bundling protein with a broad pattern of expression. As such, it is puzzling how PLS3 specifically leads to bone-related disease presentation. Our review aims to summarize the current state of knowledge regarding the function of PLS3 in the predominant cell types in the bone tissue, the osteocytes, osteoblasts and osteoclasts. This is related to the role of PLS3 in regulating mechanotransduction, calcium regulation, vesicle trafficking, cell differentiation and mineralization as part of the complex bone pathology presented by PLS3 defects. Considering the consequences of PLS3 defects on multiple aspects of bone tissue metabolism, our review motivates the study of its mechanism in bone diseases which can potentially help in the design of suitable therapy.
自 2013 年我们发现[基因名称]缺陷会导致骨骼脆弱以来，这个过程的机制细节仍然不清楚。已经确定[基因名称]变体导致综合征性和非综合征性骨质疏松症以及骨关节炎。PLS3 编码一种肌动蛋白束集蛋白，具有广泛的表达模式。因此，令人困惑的是 PLS3 如何特异性导致与骨骼相关的疾病表现。我们的综述旨在总结目前关于 PLS3 在骨骼组织中主要细胞类型——成骨细胞、成骨细胞和破骨细胞中的功能的知识状态。这与 PLS3 在调节机械转导、钙调节、囊泡运输、细胞分化和矿化中的作用有关，这些是 PLS3 缺陷所表现出的复杂骨骼病理学的一部分。考虑到 PLS3 缺陷对骨骼组织代谢多个方面的影响，我们的综述促使人们研究其在骨骼疾病中的机制，这可能有助于设计合适的治疗方法。
