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