Akkiraju Hemanth, Nohe Anja
Biological Sciences, University of Delaware, Newark, DE 19716, USA.
J Dev Biol. 2015 Dec;3(4):177-192. doi: 10.3390/jdb3040177. Epub 2015 Dec 18.
Articular cartilage (AC) covers the diarthrodial joints and is responsible for the mechanical distribution of loads across the joints. The majority of its structure and function is controlled by chondrocytes that regulate Extracellular Matrix (ECM) turnover and maintain tissue homeostasis. Imbalance in their function leads to degenerative diseases like Osteoarthritis (OA). OA is characterized by cartilage degradation, osteophyte formation and stiffening of joints. Cartilage degeneration is a consequence of chondrocyte hypertrophy along with the expression of proteolytic enzymes. Matrix Metalloproteinases (MMPs) and A Disintegrin and Metalloproteinase with Thrombospondin Motifs (ADAMTS) are an example of these enzymes that degrade the ECM. Signaling cascades involved in limb patterning and cartilage repair play a role in OA progression. However, the regulation of these remains to be elucidated. Further the role of stem cells and mature chondrocytes in OA progression is unclear. The progress in cell based therapies that utilize Mesenchymal Stem Cell (MSC) infusion for cartilage repair may lead to new therapeutics in the long term. However, many questions are unanswered such as the efficacy of MSCs usage in therapy. This review focuses on the role of chondrocytes in cartilage formation and the progression of OA. Moreover, it summarizes possible alternative therapeutic approaches using MSC infusion for cartilage restoration.
关节软骨覆盖在滑膜关节表面,负责在关节间机械性地分配负荷。其大部分结构和功能由软骨细胞控制,软骨细胞调节细胞外基质(ECM)的周转并维持组织稳态。它们功能的失衡会导致骨关节炎(OA)等退行性疾病。OA的特征是软骨退化、骨赘形成和关节僵硬。软骨退化是软骨细胞肥大以及蛋白水解酶表达的结果。基质金属蛋白酶(MMPs)和含血小板反应蛋白基序的解聚素和金属蛋白酶(ADAMTS)就是这些降解ECM的酶的例子。参与肢体模式形成和软骨修复的信号级联在OA进展中起作用。然而,这些信号级联的调控仍有待阐明。此外,干细胞和成熟软骨细胞在OA进展中的作用尚不清楚。利用间充质干细胞(MSC)输注进行软骨修复的细胞疗法的进展可能会在长期内带来新的治疗方法。然而,许多问题尚未得到解答,例如MSC在治疗中的疗效。本综述重点关注软骨细胞在软骨形成和OA进展中的作用。此外,它总结了使用MSC输注进行软骨修复的可能替代治疗方法。