中国组织工程研究

中国组织工程研究 ›› 2026, Vol. 30 ›› Issue (14): 3576-3585.doi: 10.12307/2026.078

• 纳米生物材料 nanobiomaterials • 上一篇    

介孔ZLN005@聚多巴胺纳米颗粒对骨关节炎软骨细胞的保护作用

吴天翼1，缪逸鸣2，万恺晨1，滕  云1，邹  俊1   

  1. 1苏州大学附属第一医院，江苏省苏州市   215006；2江苏省常熟市中医院，江苏省常熟市   215500
  • 收稿日期:2025-03-14 接受日期:2025-05-18 出版日期:2026-05-18 发布日期:2025-09-10
  • 通讯作者: 邹俊，博士，主任医师，苏州大学附属第一医院骨科，江苏省苏州市 215006
  • 作者简介:吴天翼，男，1998年生，江苏省宜兴市人，汉族，苏州大学在读硕士，主要从事脊柱外科、组织工程方面的研究。
  • 基金资助:
    国家自然科学基金项目(82172506)，项目负责人：邹俊

Protective effect of mesoporous ZLN005@polydopamine nanoparticles on chondrocytes in osteoarthritis

Wu Tianyi1, Miao Yiming2, Wan Kaichen1, Teng Yun1, Zou Jun1    

  1. 1First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China; 2Changshu Municipal Hospital of Traditional Chinese Medicine, Changshu 215500, Jiangsu Province, China
  • Received:2025-03-14 Accepted:2025-05-18 Online:2026-05-18 Published:2025-09-10
  • Contact: Zou Jun, MD, Chief physician, First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China
  • About author:Wu Tianyi, Master candidate, First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China
  • Supported by:
    National Natural Science Foundation of China, No. 82172506 (to ZJ)

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摘要：

文题释义：
ZLN005：是过氧化物酶体增殖物激活受体γ辅激活因子1α激动剂，能够增强过氧化物酶体增殖物激活受体γ辅激活因子1α的转录活性，达到维护线粒体稳态的效果。
聚多巴胺纳米颗粒：是由多巴胺单体在碱性环境下自聚合而成的纳米级颗粒，通常具有均匀的尺寸分布和表面丰富的官能团、优异的生物相容性和可降解性，作为一种理想的药物载体被广泛用于生物工程。

背景：现有研究普遍认为线粒体功能障碍和基质代谢失衡是导致骨关节炎进展的关键因素。ZLN005是过氧化物酶体增殖物激活受体γ辅激活因子1α激动剂，在炎症环境中可维护线粒体稳态。
目的：探索介孔ZLN005@聚多巴胺纳米颗粒对骨关节炎软骨细胞的保护作用。
方法：①在加入或不加入白细胞介素1β条件下，观察5，10，20 μmol/L ZLN005对第4代小鼠软骨细胞增殖的影响。在加入白细胞介素1β条件下，观察10，20 μmol/L ZLN005对第4代小鼠软骨细胞聚集蛋白多糖、Ⅱ型胶原蛋白、SOX9、基质金属蛋白酶13、基质金属蛋白酶3、血小板反应蛋白解整合素金属肽酶5 mRNA与蛋白表达的影响。②制备介孔ZLN005@聚多巴胺纳米颗粒，表征纳米颗粒的微观形貌、水合粒径、多分散指数与体外药物释放。将不同质量浓度介孔ZLN005@聚多巴胺纳米颗粒与第4代小鼠软骨细胞共培养，CCK-8与活死染色检测细胞增殖。在加入白细胞介素1β条件下，观察介孔聚多巴胺纳米颗粒、ZLN005、介孔ZLN005@聚多巴胺纳米颗粒对第4代小鼠软骨细胞聚集蛋白多糖、Ⅱ型胶原蛋白、SOX9、基质金属蛋白酶13、基质金属蛋白酶3、血小板反应蛋白解整合素金属肽酶5蛋白表达的影响。
结果与结论：①在加入或不加入白细胞介素1β条件下，不同浓度ZLN005均未影响小鼠软骨细胞的增殖。在加入白细胞介素1β条件下，10，20 μmol/L ZLN005均可提升聚集蛋白多糖、Ⅱ型胶原蛋白、SOX9表达，降低基质金属蛋白酶13、基质金属蛋白酶3表达，并且以20 μmol/L ZLN005的作用效果更显著。②介孔ZLN005@聚多巴胺纳米颗粒呈现均一的球形结构，平均直径约350 nm，可见明显的介孔结构，多分散指数为0.09，体外可缓慢持续释放ZLN005。5-100 μg/mL介孔ZLN005@聚多巴胺纳米颗粒不影响小鼠软骨细胞的增殖。在加入白细胞介素1β条件下，ZLN005、介孔ZLN005@聚多巴胺纳米颗粒可提高聚集蛋白多糖、Ⅱ型胶原蛋白、SOX9蛋白表达，降低基质金属蛋白酶13、基质金属蛋白酶3、血小板反应蛋白解整合素金属肽酶5蛋白表达，并且介孔ZLN005@聚多巴胺纳米颗粒的作用更明显。结果表明介孔ZLN005@聚多巴胺纳米颗粒可调节骨关节炎软骨细胞的基质代谢，发挥保护作用。
https://orcid.org/0000-0002-5549-6272 (吴天翼) 

中国组织工程研究杂志出版内容重点：生物材料；骨生物材料；口腔生物材料；纳米材料；缓释材料；材料相容性；组织工程

关键词: 软骨细胞">, 纳米颗粒">, 聚多巴胺">, ZLN005">, 基质代谢">, 骨关节炎">, 工程化骨材料

Abstract: BACKGROUND: Existing studies generally believe that mitochondrial dysfunction and matrix metabolism imbalance are key factors leading to the progression of osteoarthritis. ZLN005 is a peroxisome proliferator-activated receptor γ coactivator 1α agonist that can maintain mitochondrial homeostasis in an inflammatory environment.
OBJECTIVE: To explore the protective effect of mesoporous ZLN005@polydopamine nanoparticles on osteoarthritis chondrocytes. 
METHODS: (1) The effects of 5, 10, and 20 μmol/L ZLN005 on the proliferation of passage 4 mouse chondrocytes were observed with or without the addition of interleukin-1β. The effects of 10 and 20 μmol/L ZLN005 on the mRNA and protein expressions of aggrecan, type II collagen, SOX9, matrix metalloproteinase 13, matrix metalloproteinase 3, and thrombospondin integrin metallopeptidase 5 in passage 4 mouse chondrocytes were observed with the addition of interleukin-1β. (2) Mesoporous ZLN005@polydopamine nanoparticles were prepared, and the microscopic morphology, hydration particle size, polydispersity index and in vitro drug release of the nanoparticles were characterized. Mesoporous ZLN005@polydopamine nanoparticles of different mass concentrations were co-cultured with passage 4 mouse chondrocytes, and cell proliferation was detected by CCK-8 assay and live-dead staining. Under the condition of adding interleukin-1β, the effects of mesoporous polydopamine nanoparticles, ZLN005, and mesoporous ZLN005@polydopamine nanoparticles on the expression of aggrecan, type II collagen, SOX9, matrix metalloproteinase 13, matrix metalloproteinase 3, and thrombospondin integrin metallopeptidase 5 proteins in passage 4 mouse chondrocytes were observed. 
RESULTS AND CONCLUSION: (1) With or without the addition of interleukin-1β, different concentrations of ZLN005 did not affect the proliferation of mouse chondrocytes. When interleukin-1β was added, 10 and 20 μmol/L ZLN005 could increase the expression of aggrecan, type II collagen, and SOX9, and reduce the expression of matrix metalloproteinase 13 and matrix metalloproteinase 3, and the effect of 20 μmol/L ZLN005 was more significant. (2) Mesoporous ZLN005@polydopamine nanoparticles showed a uniform spherical structure with an average diameter of about 350 nm, with obvious mesoporous structure and a polydispersity index of 0.09. ZLN005 could be slowly and continuously released in vitro. 5-100 μg/mL mesoporous ZLN005@polydopamine nanoparticles did not affect the proliferation of mouse chondrocytes. Under the condition of adding interleukin-1β, ZLN005 and mesoporous ZLN005@polydopamine nanoparticles could increase the expression of aggrecan, type II collagen, and SOX9 protein, and reduce the expression of matrix metalloproteinase 13, matrix metalloproteinase 3, and thrombospondin integrin metallopeptidase 5 protein, and the effect of mesoporous ZLN005@polydopamine nanoparticles was more obvious. The results show that mesoporous ZLN005@polydopamine nanoparticles can regulate the matrix metabolism of osteoarthritis chondrocytes and play a protective role. 

Key words: chondrocyte">, nanoparticle">, polydopamine">, ZLN005">, matrix metabolism">, osteoarthritis">, engineered bone material

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