title: The impact of forced joint exercise on lubricin biosynthesis from articular cartilage following ACL transection and intra-articular lubricin's effect in exercised joints following ACL transection.
abstract: OBJECTIVE
  To evaluate the impact of forced joint exercise following acute knee injury on lubricin metabolism and its relationship to cartilage degeneration and to assess chondroprotection of a single-dose purified human lubricin injection in exercised injured joints.
  
  
  METHODS
  Anterior cruciate ligament transection (ACLT) was performed in rats with six experimental groups; 3-week post-ACLT, 3-week post-ACLT + exercise, 5-week post-ACLT, 5-week post-ACLT + exercise, and 5-week post-ACLT + exercise treated with intra-articular phosphate buffered saline (PBS) or lubricin. Joint exercise was achieved using a rotating cylinder at a speed of 6 rpm for 30 min daily, 5 days a week starting 1 week following surgery. Cartilage lubricin expression in injured joints was determined. Histological analyses included Safranin O/Fast Green, activated caspase-3, and lubricin mRNA in-situ hybridization. Assessment of cartilage damage was performed by osteoarthritis research society international (OARSI) modified Mankin scoring and urinary CTXII (uCTXII) levels.
  
  
  RESULTS
  At 3 weeks, lubricin expression in exercised ACLT joints was significantly (P < 0.001) lower compared to ACLT joints. The OARSI scores were significantly (P < 0.001) higher in the ACLT + exercise animals compared to ACLT animals at 5 weeks. Compared to 3-week ACLT, 3-week ACLT + exercise cartilage showed increased caspase-3 staining. Compared to ACLT + exercise and PBS-treated ACLT + exercise, lubricin intra-articular treatment resulted in a significant increase (P < 0.001) in cartilage lubricin gene expression and a reduction (P < 0.05) in uCTXII levels.
  
  
  CONCLUSIONS
  Joint exercise resulted in decreased lubricin cartilage expression, increased cartilage degeneration and reduced superficial zone chondrocyte viability in the ACLT joint. Intra-articular lubricin administration ameliorated cartilage damage due to exercise and preserved superficial zone chondrocytes' viability.
authors.affiliation: Department of Pharmaceutical Sciences, Massachusetts College of Pharmacy and Health Sciences, Boston, MA 02115, USA. khaled.elsaid@mcphs.edu
authors.forename: K A
authors.initials: KA
authors.lastname: Elsaid
authors.forename: L
authors.initials: L
authors.lastname: Zhang
authors.forename: K
authors.initials: K
authors.lastname: Waller
authors.forename: J
authors.initials: J
authors.lastname: Tofte
authors.forename: E
authors.initials: E
authors.lastname: Teeple
authors.forename: B C
authors.initials: BC
authors.lastname: Fleming
authors.forename: G D
authors.initials: GD
authors.lastname: Jay
mesh_terms: D000818:Animals; D016118:Anterior Cruciate Ligament / Q000378:metabolism; D000070598:Anterior Cruciate Ligament Injuries; D002358:Cartilage, Articular / Q000378:metabolism* / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D019902:Chondrocytes / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D015444:Exercise; D006023:Glycoproteins / Q000378:metabolism* / Q000494:pharmacology; D006614:Hindlimb / Q000473:pathology; D006801:Humans; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew; D000099158:Proteoglycan 4
chemical_list: D053148:Caspase 3; D006023:Glycoproteins; D000099158:Proteoglycan 4