摘要
骨关节炎(OA)作为一种影响全球数亿人的主要致残性疾病,正从传统的"软骨磨损"观念转变为一种累及整个关节的复杂疾病。尽管其社会经济负担日益沉重,目前仍缺乏能逆转OA病程的临床疗法。近年来,得益于基因组学、单细胞测序和再生医学的飞速发展,OA的基础和转化研究取得了突破性进展。大规模全基因组关联分析揭示了数百个新的遗传风险位点,为药物再利用和早期预测模型的建立提供了基础。研究深入到细胞层面,发现了软骨细胞独特的生理机制,并通过单细胞图谱揭示了关节内多组织、多细胞类型(如脂肪垫、滑膜、软骨下骨)间的复杂病理通讯网络,证实了细胞衰老在OA的重要驱动作用。这些基础研究的突破正催生着创新的治疗策略,包括靶向离子通道和"肠-关节轴"的OA治疗新药,利用内源性干/祖细胞实现软骨原位再生,以及开发智能生物材料用于组织修复和靶向药物递送。未来,整合多组学数据进行精准分型与早期干预,将是开发出临床有效的OA疾病修正疗法的重要策略。
Osteoarthritis(OA),a leading cause of disability that affects hundreds of millions of people worldwide,has moved beyond the traditional concept of"wear and tear"to become a complex disease involving the entire joint.Despite its increasing socioeconomic burden,there is currently a lack of clinical therapies that can reverse the progression of OA.In recent years,foundational and translational research in OA has achieved breakthrough progress,driven by rapid advancements in genomics,single-cell sequencing,and regenerative medicine.Large-scale genome-wide association studies have identified hundreds of new genetic risk loci,providing a basis for drug repurposing and the development of early predictive models.Research has delved into the cellular level,uncovering unique physiological mechanisms of chondrocytes and revealing the complex pathological signaling networks between multiple tissues and cell types within the joint(such as the infrapatellar fat pad,synovium,and subchondral bone)through single-cell atlases,confirming the significant role of cellular senescence as a driver of OA.These fundamental research breakthroughs are spurring innovative therapeutic strategies,including new OA drugs targeting ion channels and the"gut-joint axis,"in-situ cartilage regeneration using endogenous stem/progenitor cells,and the development of smart biomaterials for tissue repair and targeted drug delivery.In the future,integrating multi-omics data for precise phenotyping and early intervention will be a key strategy for developing clinically effective disease-modifying therapies for OA.
作者
肖骏
Xiao Jun(Department of Orthopedics,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,China)
出处
《中华实验外科杂志》
2025年第11期2165-2169,共5页
Chinese Journal of Experimental Surgery
关键词
骨关节炎
软骨退变
基因组学
细胞衰老
再生医学
Osteoarthritis
Cartilage degeneration
Genomics
Cellular senescence
Regenerative medicine
