Kraeutler Matthew J, Kaenkumchorn Tanyaporn, Pascual-Garrido Cecilia, Wimmer Markus A, Chubinskaya Susanna
Department of Orthopedics, University of Colorado School of Medicine, Aurora, CO, USA.
Department of Pediatrics, Rush University Medical Center, Chicago, IL, USA.
Cartilage. 2017 Jan;8(1):12-18. doi: 10.1177/1947603516642572. Epub 2016 Apr 11.
Posttraumatic osteoarthritis (PTOA) is the most common form of osteoarthritis (OA) of the ankle joint. PTOA occurs as a result of several factors, including the poor regenerative capacity of hyaline articular cartilage as well as increased contact stresses following trauma. The purpose of this article is to review the epidemiology, pathogenesis, and potential targets for treatment of PTOA in the ankle joint. Previous reviews primarily addressed clinical approaches to ankle PTOA, while the focus of the current article will be specifically on the newly acquired knowledge of the cellular mechanisms that drive PTOA in the ankle joint and means for potential targeted therapeutics that might halt the progression of cartilage degeneration and/or improve the outcome of surgical interventions. Three experimental treatment strategies are discussed in this review: (1) increasing the anabolic potential of chondrocytes through treatment with growth factors such as bone morphogenetic protein-7; (2) limiting chondrocyte cell death either through the protection of cell membrane with poloxamer 188 or inhibiting activity of intracellular proteases, caspases, which are responsible for cell death by apoptosis; and (3) inhibiting catabolic/inflammatory responses of chondrocytes by treating them with anti-inflammatory agents such as tumor necrosis factor-α antagonists. Future studies should focus on identifying the appropriate timing for treatment and an appropriate combination of anti-inflammatory, chondro- and matrix-protective biologics to limit the progression of trauma-induced cartilage degeneration and prevent the development of PTOA in the ankle joint.
创伤后骨关节炎(PTOA)是踝关节骨关节炎(OA)最常见的形式。PTOA的发生是多种因素作用的结果,包括透明关节软骨再生能力差以及创伤后接触应力增加。本文旨在综述踝关节PTOA的流行病学、发病机制及潜在治疗靶点。以往的综述主要讨论踝关节PTOA的临床治疗方法,而本文的重点将特别关注驱动踝关节PTOA的细胞机制的最新知识,以及可能阻止软骨退变进展和/或改善手术干预效果的潜在靶向治疗方法。本综述讨论了三种实验性治疗策略:(1)通过用骨形态发生蛋白-7等生长因子治疗来提高软骨细胞的合成代谢潜能;(2)通过用泊洛沙姆188保护细胞膜或抑制细胞内蛋白酶(半胱天冬酶,其负责细胞凋亡导致的细胞死亡)的活性来限制软骨细胞死亡;(3)用肿瘤坏死因子-α拮抗剂等抗炎剂治疗软骨细胞,抑制其分解代谢/炎症反应。未来的研究应集中于确定合适的治疗时机以及抗炎、软骨和基质保护生物制剂的合适组合,以限制创伤性软骨退变的进展并预防踝关节PTOA的发生。