Prevention of cartilage degeneration and restoration of chondroprotection by lubricin tribosupplementation in the rat following anterior cruciate ligament transection.
OBJECTIVE
To investigate whether cartilage degeneration is prevented or minimized following intraarticular injections of lubricin derived from human synoviocytes in culture, recombinant human PRG4 (rhPRG4), or human synovial fluid (SF) in a rat model of anterior cruciate ligament (ACL) injury.


METHODS
Unilateral ACL transection (ACLT) was performed in Lewis rats (n = 45). Nine animals were left untreated. The remaining rats were given intraarticular injections (50 microl/injection) of either phosphate buffered saline (PBS) (n = 9), human synoviocyte lubricin (200 microg/ml; n = 9), rhPRG4 (200 microg/ml; n = 9), or human SF lubricin (200 microg/ml; n = 9) twice weekly beginning on day 7 after injury. Joints were harvested on day 32 after injury. Histologic analysis was performed using Safranin O-fast green staining, and articular cartilage degeneration was graded using the Osteoarthritis Research Society International (OARSI)-modified Mankin criteria. Histologic specimens were immunoprobed for lubricin and sulfated glycosaminoglycans. A 24-hour urine collection was performed on days 17 and 29 postinjury, and urinary C-terminal telopeptide of type II collagen (CTX-II) levels were measured.


RESULTS
Treatment with human synoviocyte lubricin resulted in significantly lower OARSI scores for cartilage degeneration compared with no treatment or PBS treatment (P < 0.05). Increased immunostaining for lubricin in the superficial zone chondrocytes and on the surface of cartilage was observed in lubricin-treated, but not untreated or PBS-treated, joints. On day 17, urinary CTX-II levels in human synoviocyte lubricin- and human SF lubricin-treated animals were significantly lower than those in untreated animals (P = 0.005 and P = 0.002, respectively) and in PBS-treated animals (P = 0.002 and P < 0.001, respectively).


CONCLUSIONS
After treatment with any of the 3 types of lubricin evaluated in this study, a reduction in cartilage damage following ACLT was evident, combined with a reduction in type II collagen degradation. Our findings indicate that intraarticular lubricin injection following an ACL injury may be beneficial in retarding the degeneration of cartilage and the development of posttraumatic OA.
Jay
Gregory D
GD
Warren Alpert Medical School, Brown University, Providence, Rhode Island, USA. gregory_jay_md@brown.edu
Fleming
Braden C
BC
Watkins
Bryn A
BA
McHugh
Karen A
KA
Anderson
Scott C
SC
Zhang
Ling X
LX
Teeple
Erin
E
Waller
Kimberly A
KA
Elsaid
Khaled A
KA
D000818:Animals; D016118:Anterior Cruciate Ligament / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D000070598:Anterior Cruciate Ligament Injuries; D002358:Cartilage, Articular / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D019902:Chondrocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D024043:Collagen Type II / Q000378:metabolism; D019610:Cytoprotection / Q000187:drug effects*; D006023:Glycoproteins / Q000378:metabolism / Q000494:pharmacology*; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D007270:Injections, Intra-Articular; D007719:Knee Joint / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D011897:Random Allocation; D051381:Rats; D011917:Rats, Inbred Lew; D000099158:Proteoglycan 4
D024043:Collagen Type II; D006023:Glycoproteins; D000099158:Proteoglycan 4