趋势决定进展：动态对比软骨细胞空间结构模式与biomarkers变动趋势在OA防控中的潜在作用研究

Osteoarthritis (OA) is the main cause of loss of work ability and declined quality of life for middle-aged and elderly population, which leads to heavy burden on family and social medical resources and the consumption of productivity. However, the studies focusing on the prevention and control strategy of OA based on monitoring indexes remain at a relatively low level. Recently, OA cartilage aggregation studies related to spatial organisation of joint surface chondrocytes and biomarker detection which objectively reflect the metabolism of OA bone and cartilage have captivated widespread interests from the scholars, which are becoming a novel focus of prevention and control of OA-related diseases. In China, no scholars have attempted to apply dynamic comparison of the spatial organisation of joint surface chondrocytes and the changing tendency of biomarkers to monitor the progression of OA. Few cross-sectional investigations have been conducted abroad. Prospective cohort studies with a higher level of evidence are urgently to be performed, which validate the feasibility of utilizing dynamic comparison of spatial organisation of joint surface chondrocytes and changing tendency of biomarkers as the indexes predicting OA joint injury and progression, and provide novel thinking for multi-index evaluation of OA prevention and control. Based upon previous outcomes of biomarker screening, three specific populations will be selected for this 4-year prospective cohort study. A new analysis dimension is introduced to explore the mode of articular cartilage aggregation by constructing spatial spot network. It is also designed to evaluate the dynamic space and time process of cell proliferation, migration, apoptosis, necrosis and phenotype transition and establish individualized effect model of multiple influencing factors, levels and modes. It aims to perform dynamic comparison of cartilage aggregation mode and the changing tendency of biomarkers along with concomitant variables and the hinting effect upon progress of OA, evaluate their potential value in the prevention and control strategy of OA, thereby providing stratified (group) individualized prevention and treatment for the population with a high risk of OA.

骨关节炎(OA)是中老年人群劳动力丧失和生活质量下降的主要原因之一，涉及巨大的家庭、社会医疗资源投入和生产力消耗，但基于客观监测指标的OA防控策略研究仍处于较低水平。国内目前尚没有将动态对比关节软骨细胞空间结构模式与biomarkers变动趋势用于OA监测的文献，国际上为数不多的文献也是横断面研究，缺乏证据级别更高的前瞻性队列研究资料，是否可以将动态对比软骨细胞空间结构与biomarkers变动趋势作为预测OA病程进展的指标，为OA防控策略研究的多指标评价提供了新的思路。本项目拟选取3种特定人群进行为期4年的前瞻性队列研究，通过空间点格局构建来探索关节软骨细胞聚集模式，建立可兼顾多个影响因素的多层次、多状态个体效应模型，动态对比不同分层条件下关节软骨细胞空间结构模式及biomarkers随协变量影响的变化趋势，评价其在OA防控中的潜在价值，进而为高危人群提供分层（群）预警的个体化防治方案。

骨关节炎（OA）病因复杂，病理变化涉及滑膜、肌肉、肌腱、血管、软骨、骨等多种组织结构，其所导致的关节损伤更可发生于软骨和骨等多种关节组织基质成分合成和分解过程的任意阶段，对OA高危人群的管理，涉及巨大的家庭、社会医疗资源投入和生产力的消耗，但目前针对该病的个性化的防控策略却仍处于较低的水平。OA的防控其实不仅仅是一个医学问题，还与政治、经济等社会问题密切相关。本课题评价了在不同状态、不同阶段OA患者的软骨细胞超微结构，进而对OA的病程进展及结局进行预测，再结合可以在一定程度上反映骨与软骨代谢情况和损伤程度的biomarkers，所获得资料更能从发病机制的层面OA预测OA的进展与严重程度。本研究发现，基于软骨细胞超微结构及空间结构模式等影像学检查结果结合CS、CTX-Ⅱ、DCN等biomarkers指标的动态变化评价的OA防控策略具有其特殊的优势和良好的应用前景，但有关OA防控策略的制定实际上受到很多混杂因素的影响，任何关于防控策略的客观指标都必须被放在更广泛的环境下以更审慎的态度进行使用，因此，将该研究结论广泛应用于人群干预之前在特异性和灵敏度方面尚需要有更确切的循证医学证据。本课题组认为，基于软骨细胞超微结构及空间结构模式等影像学检查结果结合biomarkers动态变化指标的个性化防控策略将是未来防控该病的一个重要方向。如在后续研究中能解决好以下问题，基于研究结论的OA防控策略将有重要的应用前景。①需建立对软骨细胞超微结构及空间结构模式等影像学检查结果与CS、CTX-Ⅱ、DCN等biomarkers指标检测的金标准方法及分级分度标准。②课题关注指标反映的是一个累积损害结果，需进一步完善这些指标的短期评价体系。综上所述，课题组将在后续研究中，结合先进的高通量空间分析与活细胞成像技术进一步研究骨与软骨细胞动态行为改变情况，针对OA疼痛机制、病程管理及生物学标志物的筛选和定量研究进行深入探讨，以期为更加科学的OA防控策略提供更为详实的数据与理论支持。相信基于软骨细胞超微结构与biomarkers监测数据的OA防控策略会在未来的疾病管理中发挥更加重要的作用。