Recombinant platelet-derived growth factor-BB alleviates osteoarthritis in a rat model by decreasing chondrocyte apoptosis in vitro and in vivo

J Cell Mol Med. 2021 Aug;25(15):7472-7484. doi: 10.1111/jcmm.16779. Epub 2021 Jul 11.

Abstract

Osteoarthritis (OA) is a common joint disease that mainly affects the diarthrodial joints. Treatments for OA include non-pharmacological interventions, topical and oral therapies, intra-articular therapies and joint surgery. However, all the treatments mentioned above mainly aim to control the symptoms instead of improving or reversing the joint condition. In this research, we observed the effect of recombinant platelet-derived growth factor (PDGF)-BB on OA in a monosodium iodoacetate (MIA)-induced rat model and revealed the possible mechanisms. In vitro, the level of inflammation in the chondrocytes was gradually alleviated, and the apoptosis rate was gradually decreased by PDGF-BB at increasing concentrations. The levels of p-p38, Bax and caspase-3 decreased, and the level of p-Erk increased with increasing PDGF-BB concentration. In vivo, PDGF-BB could significantly reverse chondrocyte and matrix loss. Furthermore, high concentrations of PDGF-BB could alleviate cartilage hyperplasia to remodel the tissue. The level of collagen II was up-regulated, and the levels of collagen X and apoptosis were down-regulated by increasing concentrations of PDGF-BB. In conclusion, recombinant PDGF-BB alleviated OA by down-regulating caspase-3-dependent apoptosis. The effects of PDGF-BB on OA mainly include inhibiting chondrocyte loss, reducing cartilage hyperplasia and osteophyte formation, and regulating collagen anabolism.

Keywords: apoptosis; knee; osteoarthritis; platelet-derived growth factor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis*
  • Becaplermin / pharmacology
  • Becaplermin / therapeutic use*
  • Caspase 3 / metabolism
  • Cells, Cultured
  • Chondrocytes / drug effects*
  • Chondrocytes / metabolism
  • Collagen / metabolism
  • Male
  • Osteoarthritis / drug therapy*
  • Rats
  • Rats, Sprague-Dawley
  • Recombinant Proteins / pharmacology
  • Recombinant Proteins / therapeutic use
  • bcl-2-Associated X Protein / metabolism
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Recombinant Proteins
  • bcl-2-Associated X Protein
  • Becaplermin
  • Collagen
  • p38 Mitogen-Activated Protein Kinases
  • Caspase 3