Liu Sijia, Deng Huili, Liu Junjie, Zhang Jun, Chen Xier, Zhou Xuchang, Zheng Chengqiang
School of Sports and Health, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
Department of Rehabilitation Medicine, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China.
Front Cell Dev Biol. 2025 Jun 10;13:1602240. doi: 10.3389/fcell.2025.1602240. eCollection 2025.
Bone metabolic diseases are typically caused by abnormal cell metabolism and cell death within the bone, involving cell types such as osteoblasts, osteoclasts, osteocytes, chondrocytes, and bone marrow mesenchymal stem cells. Bone metabolic diseases include autosomal recessive (ARO), osteosarcoma (OS), rheumatoid arthritis (RA), and osteoporosis (OP). However, there are other categories of bone metabolic disorders in addition to the four mentioned in this review, including, but not limited to, osteochondrosis, Paget's disease, and hyperparathyroidism-associated bone disease, and others. The incidence of bone metabolism-related diseases has gradually increased over time and social changes, affecting a wider and wider group of people. Therefore, systematically analyzing the molecular pathological mechanisms of bone metabolic diseases, particularly the spatiotemporal dynamics of key regulatory nodes, has become an urgent need for developing novel therapeutic strategies. It is important to note that strictly speaking OS and RA are not usually categorized as bone metabolic disorders. However, this review categorizes them as bone metabolic diseases because of the pathological mechanisms, cellular metabolic abnormalities, and clinical evidence explored in OS and RA. Both OS and RA fit the basic profile of bone metabolic diseases. SNX10, as a member of the sorting nexin family, exerts unique regulatory functions in membrane transport through its phospholipid-binding properties mediated by the PX (phox homology) domain. Recent mechanistic analyses have shown that SNX10 exhibits multidimensional therapeutic potential in bone metabolic diseases by regulating pathways such as vesicle transport, lysosome maturation, and RANKL signal transduction. This review systematically integrates the latest research evidence on SNX10 in bone metabolic diseases, focusing on elucidating its molecular regulatory networks in conditions such as ARO, OS, RA, and OP, aiming to provide a theoretical basis for the application of SNX10-targeted precision therapeutic strategies in bone metabolic diseases.
骨代谢疾病通常由骨内细胞代谢异常和细胞死亡引起，涉及成骨细胞、破骨细胞、骨细胞、软骨细胞和骨髓间充质干细胞等细胞类型。骨代谢疾病包括常染色体隐性遗传性骨硬化症（ARO）、骨肉瘤（OS）、类风湿性关节炎（RA）和骨质疏松症（OP）。然而，除了本综述中提到的四种疾病外，还有其他类型的骨代谢紊乱，包括但不限于骨软骨病、佩吉特病和甲状旁腺功能亢进相关骨病等。随着时间的推移和社会变迁，骨代谢相关疾病的发病率逐渐上升，影响的人群越来越广泛。因此，系统分析骨代谢疾病的分子病理机制，尤其是关键调控节点的时空动态，已成为开发新型治疗策略的迫切需求。需要注意的是，严格来说，骨肉瘤和类风湿性关节炎通常不被归类为骨代谢紊乱疾病。然而，由于在骨肉瘤和类风湿性关节炎中探索的病理机制、细胞代谢异常和临床证据，本综述将它们归类为骨代谢疾病。骨肉瘤和类风湿性关节炎均符合骨代谢疾病的基本特征。分选衔接蛋白10（SNX10）作为分选衔接蛋白家族的一员，通过其由PX（phox同源）结构域介导的磷脂结合特性，在膜转运中发挥独特的调控功能。最近的机制分析表明，SNX10通过调节囊泡运输、溶酶体成熟和RANKL信号转导等途径，在骨代谢疾病中展现出多维治疗潜力。本综述系统整合了关于SNX10在骨代谢疾病方面的最新研究证据，着重阐明其在常染色体隐性遗传性骨硬化症、骨肉瘤、类风湿性关节炎和骨质疏松症等病症中的分子调控网络，旨在为针对SNX10的精准治疗策略在骨代谢疾病中的应用提供理论依据。
