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

Wu Tianyi; Miao Yiming; Wan Kaichen; Teng Yun; Zou Jun

doi:10.12307/2026.078

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.