CKIP-1-Loaded Cartilage-Affinitive Nanoliposomes Reverse Osteoarthritis by Restoring Chondrocyte Homeostasis

ACS Biomater Sci Eng. 2024 Jul 8;10(7):4437-4451. doi: 10.1021/acsbiomaterials.4c00222. Epub 2024 Jun 17.

Abstract

Osteoarthritis (OA) is a chronic joint disease characterized by cartilage imbalance and disruption of cartilage extracellular matrix secretion. Identifying key genes that regulate cartilage differentiation and developing effective therapeutic strategies to restore their expression is crucial. In a previous study, we observed a significant correlation between the expression of the gene encoding casein kinase-2 interacting protein-1 (CKIP-1) in the cartilage of OA patients and OA severity scores, suggesting its potential involvement in OA development. To test this hypothesis, we synthesized a chondrocyte affinity plasmid, liposomes CKIP-1, to enhance CKIP-1 expression in chondrocytes. Our results demonstrated that injection of CAP-Lipos-CKIP-1 plasmid significantly improved OA joint destruction and restored joint motor function by enhancing cartilage extracellular matrix (ECM) secretion. Histological and cytological analyses confirmed that CKIP-1 maintains altered the phosphorylation of the signal transduction molecule SMAD2/3 of the transforming growth factor-β (TGF-β) pathway by promoting the phosphorylation of the 8T, 416S sit. Taken together, this work highlights a novel approach for the precise modulation of chondrocyte phenotype from an inflammatory to a noninflammatory state for the treatment of OA and may be broadly applicable to patients suffering from other arthritic diseases.

Keywords: casein kinase-2 interacting protein-1 (CKIP-1); cationic liposomes; chondrocytes; osteoarthritis (OA); targeted therapy.

MeSH terms

  • Animals
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Cartilage, Articular / metabolism
  • Cartilage, Articular / pathology
  • Chondrocytes* / metabolism
  • Extracellular Matrix / metabolism
  • Homeostasis*
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Liposomes* / chemistry
  • Male
  • Nanoparticles / chemistry
  • Nanoparticles / therapeutic use
  • Osteoarthritis* / metabolism
  • Osteoarthritis* / pathology
  • Osteoarthritis* / therapy
  • Phosphorylation
  • Plasmids / genetics
  • Signal Transduction
  • Smad2 Protein / metabolism
  • Smad3 Protein / genetics
  • Smad3 Protein / metabolism
  • Transforming Growth Factor beta / metabolism

Substances

  • Liposomes
  • Carrier Proteins
  • Transforming Growth Factor beta
  • Smad3 Protein
  • Smad2 Protein
  • Intracellular Signaling Peptides and Proteins