神经生长因子在骨关节炎治疗修复中的作用与应用

Effect and application of nerve growth factor in the treatment and repair of osteoarthritis

背景:骨关节炎的病理改变为软骨退变,当前的治疗手段十分有限,随着近年来交叉学科的发展,组织工程为软骨退变的修复与重建带来了新的希望。神经生长因子在全身多系统、多器官生理和病理过程中扮演重要角色,近年来研究发现,神经生长因子与骨关节炎的发生及发展过程密切相关。目的:从神经生长因子对软骨、软骨下骨、滑膜及疼痛4方面,探讨近年来神经生长因子在骨关节炎中的研究进展。设想将神经生长因子作为组织工程中的生物活性因子或细胞因子修复骨与软骨,为治疗骨关节炎提供新的思路和想法。方法:在中国知网、万方数据库,以“神经生长因子,TrkA,骨关节炎,软骨细胞,软骨退变,软骨下骨,滑膜,疼痛”为检索词;在PubMed、Web of Science数据库上以“Nerve growth factor,TrkA,osteoarthritis,chondrocyte,Cartilage degeneration,subchondral bone,synovial,pain”为检索词,检索2010-01-01/2021-07-01收录的有关骨关节炎中神经生长因子作用机制的基础及临床研究。结果与结论:①神经生长因子可促进干细胞分化、维持软骨细胞表型,促进软骨细胞表达来维持软骨的特性。②神经生长因子可通过多种方式促进成骨表达,诱导或者加重骨关节炎的发生和发展,但也有研究认为,软骨下骨的修复有利于软骨的修复。③滑膜促进神经生长因子表达参与骨关节炎的疼痛,滑膜也可在炎性因子的刺激下,间接促进软骨降解的蛋白表达。④神经生长因子是引起疼痛主要的信号因子,神经生长因子抗体的使用对骨关节炎疼痛有良好的确切的效果,但严重的不良反应限制其使用,探明其发生机制,未来仍可能成为最有潜力的止痛药物。

BACKGROUND:The main pathological change of osteoarthritis is cartilage degeneration.The current means of treatment of osteoarthritis is very limited.With the development of interdisciplinary science in recent years,tissue engineering brings new hope for the repair and reconstruction of cartilage degeneration.Nerve growth factor plays an important role in the physiological and pathological processes of multiple systems and organs in the body.In recent years,it has been found that nerve growth factor is closely related to the occurrence and development of osteoarthritis.OBJECTIVE:To explore the research progress of nerve growth factor in osteoarthritis in recent years from the aspects of nerve growth factor’s effects on cartilage,subchondral bone,synovium,and pain.It was envisaged that nerve growth factor could be used as a bioactive factor or cytokine in tissue engineering to repair bone and cartilage,providing new thoughts and ideas for the treatment of osteoarthritis.METHODS:In PubMed,Web of Science,CNKI,and WanFang databases,search terms used were“nerve growth factor,TrkA,osteoarthritis,chondrocyte,cartilage degeneration,subchondral bone,synovium,pain”in English and Chinese.Basic and clinical studies on the mechanisms of nerve growth factor in osteoarthritis were searched from January 1,2010 to July 1,2021.RESULTS AND CONCLUSION:Nerve growth factor promoted the differentiation of stem cells,maintained the phenotype of chondrocytes,and promoted the expression of chondrocytes to maintain the characteristics of cartilage.Nerve growth factor promoted osteogenic expression in a variety of ways,inducing or aggravating the occurrence and development of osteoarthritis,but some studies suggest that subchondral bone repair is beneficial to cartilage repair.Synovium promoted nerve growth factor expression and participated in the pain of osteoarthritis.Synovium also indirectly promoted the expression of cartilage degradation protein under the stimulation of inflammatory factors.Nerve growth factor is the main signal factor causing pain.The use of nerve growth factor antibody has a good and definite effect on the pain of osteoarthritis,but its use is limited by serious side effects,and the mechanism of its occurrence is explored.It may still become the most potential analgesic drugs in the future.