Cai Lei, Lv Qing, Ma Ronghua, Liu Wei, Guan Yalun, Huang Zhongqiang, Liu Qingyu, Li Yunfeng, Liu Shuhua, Li Ge, Zhang Yu
Guangdong Provincial Biotechnology Research Institute (Guangdong Provincial Laboratory Animals Monitoring Center), Guangzhou, Guangdong, 510663, China.
Department of Rheumatology and Immunology, The seventh affiliated hospital, Sun Yat-sen University, Guangzhou, 518107, China.
Heliyon. 2025 Jan 8;11(2):e41706. doi: 10.1016/j.heliyon.2025.e41706. eCollection 2025 Jan 30.
Spondyloarthritis is a prevalent and persistent condition that significantly impacts the quality of life. Its intricate pathological mechanisms have led to a scarcity of animal models capable of replicating the disease progression in humans, making it a prominent area of research interest in the field. To delve into the pathological and physiological traits of spontaneous non-human primate spondyloarthritis, this study meticulously examined the disease features of this natural disease model through an array of techniques including X-ray imaging, MRI imaging, blood biochemistry, markers of bone metabolism, transcriptomics, proteomics, and metabolomics. X-ray imaging results revealed that crab-eating monkeys () with spontaneous spondyloarthritis developed bone spurs in the spine and experienced bone destruction in peripheral joints. MRI imaging further confirmed inflammatory changes in the spine and facet joints of these monkeys, along with inflammation and bone destruction in peripheral joints. Blood biochemistry analysis showed abnormalities in liver function and kidney function indicators in crab-eating monkeys with spontaneous spondyloarthritis. Analysis of bone metabolism-related markers showed a decrease in bone formation (BGP) and bone resorption (β-CTx). A thorough correlation analysis was conducted on the transcriptome and proteome expression data, revealing a significant positive correlation between the two datasets. A total of eight genes and proteins with high expression levels were identified as common to both the transcriptome and proteome. Subsequent Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed on these co-expressed genes and proteins, indicating a predominant enrichment in the IL-17 signaling pathway, with S100A8 and S100A9 identified as the core proteins. Further analysis using clinical data in conjunction with proteome data through Weighted Gene Co-expression Network Analysis (WGCNA) demonstrated a significant positive correlation between the high expression of S100A8 and S100A9 and the clinical phenotypes of spinal abnormalities, thereby corroborating the close association of S100A8 and S100A9 with the phenotype of spondyloarthritis. Human clinical studies have already established a link between S100A8 and S100A9 and autoimmune-related arthritic diseases, suggesting that the spontaneous spondyloarthritis observed in crab-eating macaques may be related to autoimmune diseases. It is hypothesized that S100A8 and S100A9 could serve as potential predictive biomarkers for spondyloarthritis in non-human primates.
脊柱关节炎是一种常见且持续存在的疾病，严重影响生活质量。其复杂的病理机制导致缺乏能够复制人类疾病进展的动物模型，使其成为该领域研究的一个突出热点。为深入探究自发性非人灵长类脊柱关节炎的病理和生理特征，本研究通过一系列技术，包括X射线成像、磁共振成像（MRI）、血液生化、骨代谢标志物、转录组学、蛋白质组学和代谢组学，细致地检查了这种自然疾病模型的疾病特征。X射线成像结果显示，患有自发性脊柱关节炎的食蟹猴在脊柱出现骨质增生，并在外周关节发生骨质破坏。MRI成像进一步证实了这些猴子脊柱和小关节的炎症变化，以及外周关节的炎症和骨质破坏。血液生化分析表明，患有自发性脊柱关节炎的食蟹猴肝功能和肾功能指标异常。骨代谢相关标志物分析显示骨形成（骨钙素）和骨吸收（β-CTX）减少。对转录组和蛋白质组表达数据进行了全面的相关性分析，结果显示这两个数据集之间存在显著正相关。共鉴定出八个在转录组和蛋白质组中均高表达的基因和蛋白质。随后对这些共表达的基因和蛋白质进行了基因本体论（GO）和京都基因与基因组百科全书（KEGG）分析，结果表明主要富集于白细胞介素-17信号通路，其中S100A8和S100A9被确定为核心蛋白。通过加权基因共表达网络分析（WGCNA）结合临床数据和蛋白质组数据进行的进一步分析表明，S100A8和S100A9的高表达与脊柱异常的临床表型之间存在显著正相关，从而证实了S100A8和S100A9与脊柱关节炎表型的密切关联。人类临床研究已经证实S100A8和S100A9与自身免疫相关的关节炎疾病之间存在联系，这表明在食蟹猕猴中观察到的自发性脊柱关节炎可能与自身免疫性疾病有关。据推测，S100A8和S100A9可能作为非人灵长类脊柱关节炎的潜在预测生物标志物。
