Effects of supplemental intra-articular lubricin and hyaluronic acid on the progression of posttraumatic arthritis in the anterior cruciate ligament-deficient rat knee.
BACKGROUND
Lubricin and hyaluronic acid lubricate articular cartilage and prevent wear. Because lubricin loss occurs after anterior cruciate ligament injury, intra-articular lubricin injections may reduce cartilage damage in the anterior cruciate ligament-deficient knee.


OBJECTIVE
This study was conducted to determine if lubricin and/or hyaluronic acid supplementation will reduce cartilage damage in the anterior cruciate ligament-deficient knee.


METHODS
Controlled laboratory study.


METHODS
Thirty-six male rats, 3 months old, underwent unilateral anterior cruciate ligament transection. They were randomized to 4 treatments: (1) saline (phosphate-buffered saline [PBS]), (2) hyaluronic acid (HA), (3) purified human lubricin (LUB), and (4) LUB and HA (LUB+HA). Intra-articular injections were given twice weekly for 4 weeks starting 1 week after surgery. Knees were harvested 1 week after the final injection. Radiographs of each limb and synovial fluid lavages were obtained at harvest. Histologic analysis was performed to assess cartilage damage using safranin O/fast green staining. Radiographs were scored for the severity of joint degeneration using the modified Kellgren-Lawrence scale. Synovial fluid levels of sulfated glycosaminoglycan, collagen II breakdown, interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and lubricin were measured using enzyme-linked immunosorbent assay (ELISA).


RESULTS
Treatment with LUB or LUB+HA significantly decreased radiographic and histologic scores of cartilage damage (P = .039 and P = .015, respectively) when compared with the PBS and HA conditions. There was no evidence of an effect of HA nor was the LUB effect HA-dependent, suggesting that the addition of HA did not further reduce damage. The synovial fluid of knees treated with LUB had significantly more lubricin in the synovial fluid at euthanasia, although there were no differences in the other cartilage metabolism biomarkers.


CONCLUSIONS
Supplemental intra-articular LUB reduced cartilage damage in the anterior cruciate ligament-transected rat knee 6 weeks after injury, while treatment with HA did not.


CONCLUSIONS
Although longer term studies are needed, intra-articular supplementation (tribosupplementation) with lubricin after anterior cruciate ligament injury may protect the articular cartilage in the anterior cruciate ligament-injured knee.
Teeple
Erin
E
Department of Orthopaedics, Brown Medical School/Rhode Island Hospital, Providence, USA.
Elsaid
Khaled A
KA
Jay
Gregory D
GD
Zhang
Ling
L
Badger
Gary J
GJ
Akelman
Matthew
M
Bliss
Thomas F
TF
Fleming
Braden C
BC
D000818:Animals; D016118:Anterior Cruciate Ligament / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000473:pathology; D000070598:Anterior Cruciate Ligament Injuries; D001168:Arthritis / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D018450:Disease Progression; D006023:Glycoproteins / Q000627:therapeutic use*; D006820:Hyaluronic Acid / Q000627:therapeutic use*; D007270:Injections, Intra-Articular; D007718:Knee Injuries / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000473:pathology; D008297:Male; D010003:Osteoarthritis / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000473:pathology; D011859:Radiography; D051381:Rats; D011917:Rats, Inbred Lew; D012720:Severity of Illness Index; D013582:Synovial Fluid / Q000737:chemistry / Q000000981:diagnostic imaging / Q000187:drug effects; D016896:Treatment Outcome; D000099158:Proteoglycan 4
D006023:Glycoproteins; D006820:Hyaluronic Acid; D000099158:Proteoglycan 4