Vonk Lucienne A
Department of Orthopaedics, University Medical Center Utrecht, Utrecht, The Netherlands.
Connect Tissue Res. 2025 Jul 21:1-6. doi: 10.1080/03008207.2025.2536153.
Progressive degradation of articular cartilage is characteristic of osteoarthritis (OA), but OA is more than a wear-and-tear disease of the cartilage.
It is a complex, multifactorial disease affecting all joint tissues, amplified by local and systemic inflammation. Chondrocytes play a crucial role in cartilage homeostasis and various molecular pathways that leading to their catabolic state have been identified. Cartilage degradation fragments and direct exposure of chondrocytes to extracellular matrix molecules provide feedback loops that further stimulate the catabolic profile. Synovial inflammation and subchondral bone changes enhance cartilage degradation by changing the joint environment, secreting pro-inflammatory cytokines and proteolytic enzymes, and attracting immune cells. The heterogeneity of the disease is underscored by the recognition on various phenotypes and endotypes, although consensus on classification of subtypes is lacking.
In the last 25 years, we have learned that timely treatment of joint injuries and repairing the meniscus are the best options to delay cartilage degradation and the development of post-traumatic OA. In addition, clinical studies have shown that cartilage thickness can be restored, but it does not necessarily provide clinical improvements.
So far, there is no disease modifying OA drug (DMOAD) available. The development of DMOADs is partially hindered by the requirement of long preclinical and clinical studies, as cartilage degradation is a slow process. Availability of biomarkers as surrogate endpoint could accelerate the development. Biomarker panels for early diagnosis and patient stratification could also advance the field.
Currently emerging treatment approaches, such as using regenerative medicine, promising for successful treatment.
关节软骨的进行性退化是骨关节炎（OA）的特征，但OA不仅仅是软骨的磨损性疾病。
它是一种复杂的多因素疾病，影响所有关节组织，并因局部和全身炎症而加剧。软骨细胞在软骨稳态中起关键作用，并且已经确定了导致其分解代谢状态的各种分子途径。软骨降解片段以及软骨细胞直接暴露于细胞外基质分子提供了进一步刺激分解代谢特征的反馈回路。滑膜炎症和软骨下骨变化通过改变关节环境、分泌促炎细胞因子和蛋白水解酶以及吸引免疫细胞来增强软骨降解。尽管缺乏关于亚型分类的共识，但对各种表型和内型的认识强调了该疾病的异质性。
在过去25年中，我们了解到及时治疗关节损伤和修复半月板是延缓软骨降解和创伤后OA发展的最佳选择。此外，临床研究表明软骨厚度可以恢复，但不一定能带来临床改善。
到目前为止，还没有可用的改善病情的OA药物（DMOAD）。由于软骨降解是一个缓慢的过程，DMOAD的开发部分受到长期临床前和临床研究要求的阻碍。作为替代终点的生物标志物的可用性可以加速开发。用于早期诊断和患者分层的生物标志物组合也可以推动该领域的发展。
目前正在出现的治疗方法，如使用再生医学，有望取得成功治疗。
