Prevention of cartilage degeneration in a rat model of osteoarthritis by intraarticular treatment with recombinant lubricin

Arthritis Rheum. 2009 Mar;60(3):840-7. doi: 10.1002/art.24304.


Objective: Lubricin, also referred to as superficial zone protein and PRG4, is a synovial glycoprotein that supplies a friction-resistant, antiadhesive coating to the surfaces of articular cartilage, thereby protecting against arthritis-associated tissue wear and degradation. This study was undertaken to generate and characterize a novel recombinant lubricin protein construct, LUB:1, and to evaluate its therapeutic efficacy following intraarticular delivery in a rat model of osteoarthritis (OA).

Methods: Binding and localization of LUB:1 to cartilage surfaces was assessed by immunohistochemistry. The cartilage-lubricating properties of LUB:1 were determined using a custom friction testing apparatus. A cell-binding assay was performed to quantify the ability of LUB:1 to prevent cell adhesion. Efficacy studies were conducted in a rat meniscal tear model of OA. One week after the surgical induction of OA, LUB:1 or phosphate buffered saline vehicle was administered by intraarticular injection for 4 weeks, with dosing intervals of either once per week or 3 times per week. OA pathology scores were determined by histologic analysis.

Results: LUB:1 was shown to bind effectively to cartilage surfaces, and facilitated both cartilage boundary lubrication and inhibition of synovial cell adhesion. Treatment of rat knee joints with LUB:1 resulted in significant disease-modifying, chondroprotective effects during the progression of OA, by markedly reducing cartilage degeneration and structural damage.

Conclusion: Our findings demonstrate the potential use of recombinant lubricin molecules in novel biotherapeutic approaches to the treatment of OA and associated cartilage abnormalities.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Cartilage, Articular / drug effects
  • Cartilage, Articular / injuries
  • Cartilage, Articular / pathology*
  • Cell Adhesion / drug effects
  • Disease Models, Animal
  • Disease Progression
  • Glycoproteins / administration & dosage
  • Glycoproteins / pharmacology
  • Glycoproteins / therapeutic use*
  • Injections, Intra-Articular
  • Male
  • Osteoarthritis / pathology*
  • Osteoarthritis / prevention & control*
  • Random Allocation
  • Rats
  • Rats, Inbred Lew
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / pharmacology
  • Recombinant Proteins / therapeutic use*
  • Synovial Membrane / drug effects
  • Synovial Membrane / pathology
  • Treatment Outcome


  • Glycoproteins
  • Recombinant Proteins
  • lubricin