Tribosupplementation with Lubricin in Prevention of Post-Traumatic Arthritis

Abstract

Full length recombinant human lubricin (rhPRG4) maximally reduced friction between apposed explants of bovine articular cartilage. Secretion levels exceeded 1 mg/ml when expressed by transfected CHO-M cells. This level of expression is commercially scalable and will thus enable production of a GMP protein for clinical use. A purification bioprocess utilizing anion exchange, hydroxyapatite and a hydrophobic exchange media resins achieves a high level of purity. Explants of bovine articular cartilage cultured and incubated with IL-1 followed by friction testing showed higher friction than explants not receivingIL-1. The rhPRG4 restored low friction and qualitatively restored native PRG4 expression as determined by immunohistochemistry. Cartilage from the femoral condyle shows variations in IL-1 induced elevated friction. Explants from the weight bearing region show a significant response to exogenous rhPRG4 in friction reduction from this simulated inflammatory environment. A large animal trial is now planned to test pre-GMP equivalent rhPRG4 in restoring chondroprotection in the ACL-injured joint.

Open PDF

Document Details

Document Type
Technical Report
Publication Date
Dec 01, 2015
Accession Number
AD1007149

Entities

People

  • Braden C Fleming
  • Gregory Jay

Organizations

  • Rhode Island Hospital

Tags

DTIC Thesaurus Topics

  • Arthritis
  • Arthroscopy
  • Bearings
  • Blood
  • Cartilage
  • Chemistry
  • Data Analysis
  • Diseases And Disorders
  • Friction
  • Health Services
  • Joints (Anatomy)
  • Ligaments
  • Lubrication
  • Production
  • Surgery
  • Tendons
  • Tissues

Readers

  • Analytical Chemistry
  • Cellular and Molecular Pathways of Apoptosis.
  • Immunology and Pathology