Samuels Jonathan, Krasnokutsky Svetlana, Abramson Steven B
New York University School of Medicine, New York, NY, USA.
Bull NYU Hosp Jt Dis. 2008;66(3):244-50.
While research in osteoarthritis has focused on the events that lead to the destruction of articular cartilage, recent evidence suggests that two other components of the joints-bone and synovium-also play key roles in pathogenesis. All three tissues undergo alterations in concert at the structural levels in response to mechanical stress and joint malalignment. Advanced imaging studies such as MRI support this interdependence, revealing the classical changes of joint space narrowing and cartilage degeneration as well as the more recently appreciated bone marrow lesions and synovitis that may correlate with clinical symptoms. Molecular evidence also points to a coordinated release of cytokines and other inflammatory mediators from each of the three tissues together in progression of disease, although we are still in search of biochemical signatures that will predict the subset of patients who progress more quickly-and who will provide key clues to successful molecular targets in future therapies. At this time we lack definitive evidence pointing to which, if any, of the three tissues should serve as the main target for disease modification or structure protection, although most efforts have focused on cartilage. Thus current therapies focus on controlling symptoms, while research efforts search for reliable imaging and molecular biomarkers to help guide future trials of potential disease-modifying agents.
虽然骨关节炎的研究主要集中在导致关节软骨破坏的相关事件上，但最近的证据表明，关节的另外两个组成部分——骨骼和滑膜——在发病机制中也起着关键作用。在应对机械应力和关节排列不齐时，这三种组织在结构层面会协同发生改变。诸如核磁共振成像（MRI）等先进的影像学研究证实了这种相互依存关系，不仅揭示了关节间隙变窄和软骨退变等典型变化，还发现了最近才被认识到的可能与临床症状相关的骨髓损伤和滑膜炎。分子证据也表明，在疾病进展过程中，这三种组织会共同协调释放细胞因子和其他炎症介质，尽管我们仍在寻找能够预测哪些患者病情进展更快的生化特征——这些特征将为未来治疗中的成功分子靶点提供关键线索。目前，我们缺乏确凿证据来指明这三种组织中的哪一种（如果有的话）应作为疾病改善或结构保护的主要靶点，尽管大多数研究工作都集中在软骨上。因此，当前的治疗主要侧重于控制症状，而研究工作则致力于寻找可靠的影像学和分子生物标志物，以帮助指导未来潜在疾病改善药物的试验。
