转化生长因子β亚家族调控骨关节炎中的作用

Regulatory role of transforming growth factor beta subfamily in osteoarthritis

背景:骨关节炎作为中国最常见的老年慢性退行性疾病之一,因其复杂的发病机制及细胞分子交流途径,目前尚未有行之有效的方法去延缓骨关节炎的进展。而转化生长因子β在早期关节的形成、骨和软骨的发育以及关节重塑各阶段发挥重要作用,是维持与调节关节稳态的关键因子之一。目的:综述近年来国内外关于转化生长因子β亚家族在骨关节炎的发生发展中所起到的调控作用,分析其在骨关节炎不同阶段所产生的影响,探究转化生长因子β在临床治疗骨关节炎上的应用前景,以期能为临床治疗方案提供参考。方法:应用计算机检索中国知网和PubMed数据库收录的相关文献,中文检索词为“骨关节炎,转化生长因子,信号通路,骨重塑,软骨退变,血管生成,治疗”,英文检索词为“Osteoarthritis,Transforming Growth Factor,Signaling Pathway,Bone Remodeling,Cartilage Degeneration,Angiogenesis,Treatment”,最终纳入57篇文献进行综述分析。结果与结论:(1)目前,关于骨关节炎复杂的发病机制尚未有统一定论,大量研究表明骨关节炎与细胞因子和信号通路关系密切,以转化生长因子β超家族作为其发病机制和治疗突破口的相关研究也是当前的热点。(2)转化生长因子β在早期关节软骨形成与稳态维持上起到关键作用,并对于软骨损伤修复有促进作用;而在关节成型后,转化生长因子β的保护作用会减弱甚至造成破坏效应,其双重调节作用也是目前转化为临床治疗手段的重点,需后续研究明确适用范围以制定标准。(3)高水平活性转化生长因子β在机械应力的介导下参与骨细胞、成骨细胞与破骨细胞的调控,并干预随后骨微观结构的重塑,特异性抑制剂可作为治疗疾病的靶向药物,但其作用的安全性与有效性仍需临床进一步完善。(4)血管增生可能在转化生长因子β介导软骨退变及软骨下骨重塑中提供潜在的串扰途径,异常的交流途径会进一步破坏骨软骨单元微环境的稳态从而加速骨关节炎中关键的病理学进展。(5)关于转化生长因子β在骨关节炎中的研究已经较为全面,临床应用前景广泛,目前已有相关药物处于临床试验阶段,但如何控制对其他组织的潜在影响和精准控制靶向递送等关键问题亟需解决,随着研究的深入,未来有望在延缓骨关节炎治疗方式上作出新的突破。

BACKGROUND:Osteoarthritis is one of the most common senile chronic degenerative diseases in China.Due to its complex pathogenesis and cellular molecular communication pathways,there is currently no effective method to slow down the progression of osteoarthritis.Studies have found that transforming growth factor-βis one of the key factors in the maintenance and regulation of joint stability and plays a significant role in the formation of early joints,as well as the development of bone and cartilage,and the remodeling of joints at various stages.OBJECTIVE:To review the regulatory role of the transforming growth factor-βsubfamily in the occurrence and development of osteoarthritis,both domestically and internationally in recent years,to analyze the impacts it has at different stages of osteoarthritis,and to explore the potential application prospects of transforming growth factor-βin the clinical treatment of osteoarthritis,with a view to informing clinical treatment protocols..METHODS:The relevant articles were searched by computer from CNKI Database and PubMed Database.The search terms were“osteoarthritis,transforming growth factor,signaling pathway,bone remodeling,cartilage degeneration,angiogenesis,treatment”in Chinese and English,respectively.Finally,57 articles were included for review.RESULTS AND CONCLUSION:The pathogenesis of osteoarthritis remains a subject of ongoing exploration with no unified consensus.Numerous studies highlight the close correlation between osteoarthritis and cytokines,focusing on the transforming growth factor-βsuperfamily as a pivotal mechanism and therapeutic breakthrough.Transforming growth factor-βplays a crucial role in early joint cartilage formation and maintenance,promoting cartilage repair.However,post-joint formation,its protective effect weakens,leading to potential destructive consequences.This dual regulatory role is a current clinical treatment focus,necessitating further research to delineate its application scope for standardized protocols.Highly active transforming growth factor-βparticipates in the regulation of bone cells,osteoblasts,and osteoclasts under mechanical stress,and intervenes in the subsequent remodeling of bone microstructure.Specific inhibitors present potential targeted therapeutics,yet their safety and efficacy in clinical settings require refinement.Vascular proliferation may serve as a potential disruptive pathway in transforming growth factor-β-mediated cartilage degeneration and subchondral bone remodeling.Abnormal communication pathways can further disrupt the homeostasis of the microenvironment of osteochondral units,thereby accelerating key pathological progressions of osteoarthritis.Research on transforming growth factor-βin osteoarthritic contexts is comprehensive,holding broad clinical application prospects.Drugs related to transforming growth factor-βare in clinical trial phases,but addressing potential impacts on other tissues and precise control of targeted delivery are critical concerns.As research advances,there is optimism for innovative breakthroughs in slowing the progression of osteoarthritis in the future.