Prevention of cartilage degeneration and gait asymmetry by lubricin tribosupplementation in the rat following anterior cruciate ligament transection.

Abstract

OBJECTIVE:

To investigate whether cartilage degeneration is prevented or minimized in a rat model of anterior cruciate ligament (ACL) injury following a single dose-escalated intraarticular injection of lubricin derived from human synoviocytes in culture.

METHODS:

Unilateral ACL transection (ACLT) of the right hind limb was performed in Lewis rats (n = 56). Control animals underwent a capsulotomy alone, leaving the ACL intact (n = 11). Intraarticular injections (50 μl/injection) of phosphate buffered saline (PBS; n = 14 rats) and human synoviocyte lubricin (1,600 μg/ml; n = 14 rats) were performed on day 7 postsurgery. Animals were killed on day 70 postsurgery. Histologic specimens were immunoprobed for lubricin and sulfated glycosaminoglycans. Urinary C-telopeptide of type II collagen (CTX-II) levels were measured on days 35 and 70 postsurgery. Hind limb maximum applied force was determined using a variable resistor walkway to monitor quadruped gait asymmetries.

RESULTS:

Increased immunostaining for lubricin in the superficial zone and on the surface of cartilage was observed in lubricin-treated and control animals but not in PBS-treated or untreated animals with ACLT. On days 35 and 70 after surgery, urinary CTX-II levels in human synoviocyte lubricin-treated animals were lower than in untreated and PBS-treated animals (P < 0.005 and P < 0.001, respectively). Animals with ACLT treated with human synoviocyte lubricin and control animals distributed their weight equally between hind limbs compared to PBS-treated or untreated animals (P < 0.01).

CONCLUSION:

Our findings indicate that a single intraarticular injection of concentrated lubricin following ACLT reduces type II collagen degradation and improves weight bearing in the affected rat joint. These findings support the practice of tribosupplementation with lubricin for retarding cartilage degeneration and possibly the development of posttraumatic osteoarthritis.

• Authors: Gregory D Jay, Khaled A Elsaid, Karen A Kelly, Scott C Anderson, Ling Zhang, Erin Teeple, Kimberly Waller, Braden C Fleming
• Journal: Arthritis and rheumatism (Arthritis Rheum) Vol. 64 Issue 4 Pg. 1162-71 (Apr 2012) ISSN: 1529-0131 [Electronic] United States
• PMID: 22127873 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2012 by the American College of Rheumatology.

Chemical References

• Glycoproteins
• lubricin

Topics

• Animals
• Anterior Cruciate Ligament (diagnostic imaging, drug effects, pathology)
• Anterior Cruciate Ligament Injuries
• Cartilage, Articular (diagnostic imaging, drug effects, pathology)
• Gait
• Glycoproteins (administration & dosage, therapeutic use)
• Knee Injuries (diagnostic imaging, drug therapy, pathology)
• Knee Joint (diagnostic imaging, pathology)
• Lubrication
• Male
• Radiography
• Rats
• Rats, Inbred Lew