title: Prevention of cartilage degeneration and restoration of chondroprotection by lubricin tribosupplementation in the rat following anterior cruciate ligament transection.
abstract: 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.
authors.affiliation: Warren Alpert Medical School, Brown University, Providence, Rhode Island, USA. gregory_jay_md@brown.edu
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Jay
authors.forename: Braden C
authors.initials: BC
authors.lastname: Fleming
authors.forename: Bryn A
authors.initials: BA
authors.lastname: Watkins
authors.forename: Karen A
authors.initials: KA
authors.lastname: McHugh
authors.forename: Scott C
authors.initials: SC
authors.lastname: Anderson
authors.forename: Ling X
authors.initials: LX
authors.lastname: Zhang
authors.forename: Erin
authors.initials: E
authors.lastname: Teeple
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Waller
authors.forename: Khaled A
authors.initials: KA
authors.lastname: Elsaid
mesh_terms: 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
chemical_list: D024043:Collagen Type II; D006023:Glycoproteins; D000099158:Proteoglycan 4