Dr. Flannery, Mr. Zollner, Mr. Corcoran, Mr. Root, Dr. Rivera-Bermúdez, Ms Blanchet, Dr. Morris, and Ms Glasson own stock or stock options in Wyeth.
Prevention of cartilage degeneration in a rat model of osteoarthritis by intraarticular treatment with recombinant lubricin
Article first published online: 26 FEB 2009
Copyright © 2009 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 60, Issue 3, pages 840–847, March 2009
How to Cite
Flannery, C. R., Zollner, R., Corcoran, C., Jones, A. R., Root, A., Rivera-Bermúdez, M. A., Blanchet, T., Gleghorn, J. P., Bonassar, L. J., Bendele, A. M., Morris, E. A. and Glasson, S. S. (2009), Prevention of cartilage degeneration in a rat model of osteoarthritis by intraarticular treatment with recombinant lubricin. Arthritis & Rheumatism, 60: 840–847. doi: 10.1002/art.24304
- Issue published online: 26 FEB 2009
- Article first published online: 26 FEB 2009
- Manuscript Accepted: 7 NOV 2008
- Manuscript Received: 7 MAY 2008
- Wyeth Research
- NASA Graduate Student Researchers Program. Grant Number: NNG-04GN57H
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).
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.
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.
Our findings demonstrate the potential use of recombinant lubricin molecules in novel biotherapeutic approaches to the treatment of OA and associated cartilage abnormalities.