尼尔样1型生长因子通过促进软骨生成及抗炎作用来治疗骨关节炎的潜力

Potential of Nel-like molecule 1 to treat osteoarthritis by promoting cartilage formation and anti-inflammatory effects

背景:骨关节炎是一种复杂的全关节疾病,主要影响的关节是膝关节,其次是手和髋关节,治疗上主要以缓解疼痛症状为基础,但令人遗憾的是,到目前为止还没有有效的药物可以阻止疾病的进展。最近,一种具有促软骨形成、抗炎、抗脂肪、促血管化等特性的成骨蛋白——尼尔样1型生长因子(Nel-like molecule 1,Nell-1)进入研究人员的视野,因其具有促软骨生成、抗炎的双功能特性而有希望成为改善骨关节炎病情的药物。目的:文章对骨性关节炎发病机制的新见解、Nell-1的促软骨生成能力及其分子级联信号、抗炎作用及其分子机制、现阶段Nell-1应用于骨关节炎治疗的不足之处以及Nell-1临床应用的最新进展作一综述,为骨关节炎的治疗提供新的思路。方法:检索中国知网、PubMed数据库,中文检索词为"Nell-1、骨关节炎",英文检索词为"Osteoarthritis""Nell-1 AND Osteoarthritis"。检索时间范围为1995年1月至2020年3月,主要纳入影响因子>3、与Nell-1和骨关节炎关系紧密的文章,最后纳入88篇文献进行综述。结果与结论:随着人口老龄化和肥胖症的日益增多,骨关节炎较几十年前更加普遍,因此造成了更为沉重的家庭和社会经济负担。传统的止痛方法因其不能减少炎症和软骨损伤,因此都不足以用于根治性治疗。作为临床骨科医生,充分认识理解骨关节炎的发病机制、疾病的进展及转归,开展与基因工程、组织构建的生物学技术,药剂科、分子生物学等多学科的讨论,可以帮助开发更有效的治疗方案,最终目的是解除骨关节炎患者的痛苦,减轻个人及社会的经济负担。虽然对于Nell-1在骨关节炎发病机制中的新兴作用还处于初级研究阶段,仍然存在缺乏最佳给药途径、分子机制不完全清楚、没有最佳的动物模型等不足,但其具有抗炎和促进软骨生成的双重效力,因此治疗骨关节炎具有巨大的潜力。未来的研究应进一步揭示详细的潜在机制,并优化剂量、方案和给药方法,将Nell-1对于骨关节炎的治疗潜力转化为临床实践。

BACKGROUND:Osteoarthritis is a complex total joint disease.The main affected joint is the knee joint,followed by the hand and hip joints.Treatments for osteoarthritis mainly focus on the relief of pain symptoms.Unfortunately,no drugs can stop the progression of the disease until now.Recently,an osteogenic protein with the characteristics of promoting cartilage formation,anti-inflammatory,anti-fat,and vascularization.Nel-like molecule 1(Nell-1)has attracted researchers’attentions.Because of its dual functional properties of promoting cartilage production and anti-inflammation,Nell-1 is expected to become a drug for improving the condition of osteoarthritis.OBJECTIVE:To review the pathogenesis of osteoarthritis,ability of Nell-1 to promote chondrogenesis and its molecular cascade signals,anti-inflammatory effects of Nell-1 and its molecular mechanism,Nell-1’s deficiencies in the treatment of osteoarthritis and the latest clinical application of Nell-1,thereby providing new ideas for the treatment of osteoarthritis.METHODS:CNKI and PubMed were retrieved for articles tightly related to Nell-1 and osteoarthritis with an impact factor>3 using the keywords of"Nell-1 AND Osteoarthritis,"and"Osteoarthritis"in Chinese and English,respectively.The time range for literature retrieval was from January 1995 to March 2020.Finally,88 articles were included for review.RESULTS AND CONCLUSION:With the aging of population and increasing of obesity,osteoarthritis is more common than it was a few decades ago,thus leading to a heavier family and socioeconomic burden.Traditional analgesic methods cannot be used as curative treatments because they cannot reduce inflammation and cartilage damage.It is helpful for a clinical orthopedist to develop a more effective treatment protocol by fully understanding the pathogenesis,disease progression and outcome of osteoarthritis,and initiating multidisciplinary discussions involving biological technology,pharmacology,and molecular biology related to genetic engineering and tissue construction.The ultimate goal of an effective treatment protocol is to relieve the suffering of osteoarthritis patients and to reduce the financial burden of individuals and the society.Although the emerging role of Nell-1 in the pathogenesis of osteoarthritis is still in its infancy,there are still some limitations,including a lack of the best route of administration,incomplete understanding of relevant molecular mechanisms,and no optimal animal models.However,Nell-1 has a great potential in the treatment of osteoarthritis as a result of its dual effects of anti-inflammation and promoting cartilage production.Future research should reveal detailed potential mechanisms,and optimize the dosage,regimen,and method of Nell-1 administration,with an attempt to translate Nell-1’s therapeutic potential for osteoarthritis into clinical practice.