Biological Sciences Department, College of Science, King Faisal University, Al Ahsa 31982, Saudi Arabia.
Lab of Molecular Physiology, Zoology Department, Faculty of Science, Assiut University, Assiut 71515, Egypt.
Int J Mol Sci. 2023 Feb 20;24(4):4215. doi: 10.3390/ijms24044215.
Osteoarthritis (OA) and rheumatoid arthritis (RA) are two common disorders that disrupt the quality of life of millions of people. These two chronic diseases cause damage to the joint cartilage and surrounding tissues of more than 220 million people worldwide. Sex-determining region Y-related (SRY) high-mobility group (HMG) box C, SOXC, is a superfamily of transcription factors that have been recently shown to be involved in various physiological and pathological processes. These include embryonic development, cell differentiation, fate determination, and autoimmune diseases, as well as carcinogenesis and tumor progression. The SOXC superfamily includes SOX4, SOX11, and SOX12, all have a similar DNA-binding domain, i.e., HMG. Herein, we summarize the current knowledge about the role of SOXC transcription factors during arthritis progression and their potential utilization as diagnostic biomarkers and therapeutic targets. The involved mechanistic processes and signaling molecules are discussed. SOX12 appears to have no role in arthritis, however SOX11 is dysregulated and promotes arthritic progression according to some studies but supports joint maintenance and protects cartilage and bone cells according to others. On the other hand, SOX4 upregulation during OA and RA was documented in almost all studies including preclinical and clinical models. Molecular details have indicated that SOX4 can autoregulate its own expression besides regulating the expression of SOX11, a characteristic associated with the transcription factors that protects their abundance and activity. From analyzing the currently available data, SOX4 seems to be a potential diagnostic biomarker and therapeutic target of arthritis.
骨关节炎（OA）和类风湿关节炎（RA）是两种常见的疾病，会破坏数百万人的生活质量。这两种慢性疾病会导致全球超过 2.2 亿人的关节软骨和周围组织受损。性决定区 Y 相关（SRY）高迁移率族盒 C（SOXC）是转录因子的一个超家族，最近研究表明其参与了各种生理和病理过程。这些过程包括胚胎发育、细胞分化、命运决定以及自身免疫性疾病，还有致癌作用和肿瘤进展。SOXC 超家族包括 SOX4、SOX11 和 SOX12，它们都具有相似的 DNA 结合域，即 HMG。在此，我们总结了目前关于 SOXC 转录因子在关节炎进展过程中作用的知识，以及它们作为诊断生物标志物和治疗靶点的潜在应用。讨论了涉及的机制过程和信号分子。SOX12 在关节炎中似乎没有作用，但是根据一些研究，SOX11 失调并促进关节炎进展，但根据其他研究，SOX11 支持关节维持并保护软骨和骨细胞。另一方面，几乎所有的研究（包括临床前和临床模型）都记录了 OA 和 RA 期间 SOX4 的上调。分子细节表明，SOX4 可以在调节 SOX11 表达的同时自我调节其自身的表达，这是一种与保护其丰度和活性的转录因子相关的特征。从分析目前可用的数据来看，SOX4 似乎是关节炎的一个有潜力的诊断生物标志物和治疗靶点。
