title: Prevention of cartilage degeneration in a rat model of osteoarthritis by intraarticular treatment with recombinant lubricin.
abstract: OBJECTIVE
  Lubricin, also referred to as superficial zone protein and PRG4, is a synovial glycoprotein that supplies a friction-resistant, antiadhesive coating to the surfaces of articular cartilage, thereby protecting against arthritis-associated tissue wear and degradation. This study was undertaken to generate and characterize a novel recombinant lubricin protein construct, LUB:1, and to evaluate its therapeutic efficacy following intraarticular delivery in a rat model of osteoarthritis (OA).
  
  
  METHODS
  Binding and localization of LUB:1 to cartilage surfaces was assessed by immunohistochemistry. The cartilage-lubricating properties of LUB:1 were determined using a custom friction testing apparatus. A cell-binding assay was performed to quantify the ability of LUB:1 to prevent cell adhesion. Efficacy studies were conducted in a rat meniscal tear model of OA. One week after the surgical induction of OA, LUB:1 or phosphate buffered saline vehicle was administered by intraarticular injection for 4 weeks, with dosing intervals of either once per week or 3 times per week. OA pathology scores were determined by histologic analysis.
  
  
  RESULTS
  LUB:1 was shown to bind effectively to cartilage surfaces, and facilitated both cartilage boundary lubrication and inhibition of synovial cell adhesion. Treatment of rat knee joints with LUB:1 resulted in significant disease-modifying, chondroprotective effects during the progression of OA, by markedly reducing cartilage degeneration and structural damage.
  
  
  CONCLUSIONS
  Our findings demonstrate the potential use of recombinant lubricin molecules in novel biotherapeutic approaches to the treatment of OA and associated cartilage abnormalities.
authors.affiliation: Wyeth Research, Cambridge, Massachusetts, USA. cflannery@wyeth.com
authors.forename: Carl R
authors.initials: CR
authors.lastname: Flannery
authors.forename: Richard
authors.initials: R
authors.lastname: Zollner
authors.forename: Chris
authors.initials: C
authors.lastname: Corcoran
authors.forename: Aled R
authors.initials: AR
authors.lastname: Jones
authors.forename: Adam
authors.initials: A
authors.lastname: Root
authors.forename: Moisés A
authors.initials: MA
authors.lastname: Rivera-Bermúdez
authors.forename: Tracey
authors.initials: T
authors.lastname: Blanchet
authors.forename: Jason P
authors.initials: JP
authors.lastname: Gleghorn
authors.forename: Lawrence J
authors.initials: LJ
authors.lastname: Bonassar
authors.forename: Alison M
authors.initials: AM
authors.lastname: Bendele
authors.forename: Elisabeth A
authors.initials: EA
authors.lastname: Morris
authors.forename: Sonya S
authors.initials: SS
authors.lastname: Glasson
mesh_terms: D000818:Animals; D002358:Cartilage, Articular / Q000187:drug effects / Q000293:injuries / Q000473:pathology*; D002448:Cell Adhesion / Q000187:drug effects; D004195:Disease Models, Animal; D018450:Disease Progression; D006023:Glycoproteins / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D007270:Injections, Intra-Articular; D008297:Male; D010003:Osteoarthritis / Q000473:pathology* / Q000517:prevention & control*; D011897:Random Allocation; D051381:Rats; D011917:Rats, Inbred Lew; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D013583:Synovial Membrane / Q000187:drug effects / Q000473:pathology; D016896:Treatment Outcome; D000099158:Proteoglycan 4
chemical_list: D006023:Glycoproteins; D011994:Recombinant Proteins; D000099158:Proteoglycan 4