Recent advances and applications of Kartogenin in cartilage regeneration and repair

doi:10.3969/j.issn.2095-4344.2809

Abstract

Abstract:

BACKGROUND: Cartilage defects due to cartilage lesions such as osteoarthritis are difficult to

self-regenerate. How to promote cartilage regeneration and restore smooth wound surface is a hot topic in recent years.

OBJECTIVE: To review the general concept, mechanism and effect of Kartogenin as well as the current clinical models, providing new ideas for the regeneration and repair of damaged cartilage.

METHODS: WanFang, CNKI, and PubMed were retrieved for studies on Kartogenin combined with tissue engineering in the field of cartilage regeneration and repair published from January 2010 to January 2020. The keywords were “Kartogenin, cartilage regeneration, chondrogenesis, chondroprotection” in English and “Kartogenin, cartilage regeneration and repair, cartilage protection, tissue engineering" in Chinese. After initial screening by reading titles and abstracts, irrelevant literature was excluded and finally 55 articles were included for result analysis according to the inclusion criteria and exclusion criteria.

RESULTS AND CONCLUSION: As a newly discovered small molecule, Kartogenin has better stability, lower immunogenicity and easy availability. In addition, Kartogenin plays a synergistic role with growth factors in cartilage regeneration and has great potential in cartilage formation and cartilage protection. Through in vitro experiments or animal experiments, it has been proved that Kartogenin plays a positive role in promoting cartilage generation, osteoarthritis treatment, repair of tendon and bone injury, and wound healing, and helps to protect the degeneration of cartilage and healing of rotator cuff injury. With more basic research and clinical trials on Kartogenin, a breakthrough in cartilage regeneration and repair will be made in the near future.

Key words: bone, arthritis, cartilage, cartilage degeneration, cartilage protection, pathway, factor, review

CLC Number:

Lu Junxu, Wang Yuanbo, Hu Yanuan, Yang Biaobing. Recent advances and applications of Kartogenin in cartilage regeneration and repair[J]. Chinese Journal of Tissue Engineering Research, 2020, 24(32): 5221-5227.

Figures/Tables 3

2.3.1 具有软骨再生与保护的效果 JOHNSON等[4]建立了慢性关节损伤及急性外科手术两种啮齿动物模型，并使用关节内注射KGN的方式对这两种模型进行治疗。骨关节炎患者血浆中的寡聚基质蛋白水平通常会升高[32]，JOHNSON等[4]发现注射KGN后的慢性关节损伤模型中发现外周血内的寡聚基质蛋白的水平有所下降。在接受KGN治疗的急性外科手术模型组的关节组织学评分降低了50%(基于骨关节炎研究协会国际评分系统)；另外，与对照组相比，接受KGN治疗显著缓解了骨关节炎引起的疼痛，循环中的Ⅱ型胶原片段(软骨损伤后释放的肽类物质)的水平也降低了1.8倍。这些实验均证明了KGN有促进软骨再生的作用。骨关节炎通过微骨折手术治疗可以缓解症状，但大多数新生的软骨组织会转变为纤维软骨，这种纤维软骨与透明软骨相比有所退化，且机械力学特性有明显的减弱[33]，所以微骨折手术治疗的疗效仍不能令人满意。到目前为止，尚未有治疗方法来恢复退行性软骨的细胞表型。KGN除了增强软骨生成外，还可以保持软骨细胞表型。当KGN与微骨折手术疗法相结合时，可实现透明软骨的再生。XU等[13]诱发兔髌骨沟全层软骨缺损，并将其分为2组，分别采用不同的治疗方法：第1组行微骨折手术治疗加每周关节内注射KGN处理；第2组行微骨折治疗加二甲基亚砜注射液处理。4周后，第1组中50%以上的软骨缺损被修复的组织所覆盖，而第2组只观察到少量的纤维组织；12周后，第1组中的软骨损伤处几乎痊愈，并且有接近完整的软骨表面，见图3，第1组的国际软骨修复学会和O’Driscoll得分也比第2组更高，相比之下，第2组中的软骨损伤约有80%被裂隙状表面的纤维状组织覆盖；免疫组织化学染色显示，第1组产生了大量的Ⅱ型胶原和较少的Ⅰ型胶原，而第2组仅有少量的Ⅱ型胶原和较多的Ⅰ型胶原产生。该研究证明了微骨折手术治疗加关节内注射KGN治疗软骨损伤具有软骨再生和保护的作用。 "

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