title: Blocking of tumor necrosis factor activity promotes natural repair of osteochondral defects in rabbit knee.
abstract: OBJECTIVE
  Osteochondral defects have a limited capacity for repair. We therefore investigated the effects of tumor necrosis factor (TNF) signal blockade by etanercept (human recombinant soluble TNF receptor) on the repair of osteochondral defects in rabbit knees.
  
  
  METHODS
  Osteochondral defects (5 mm in diameter) were created in the femoral patellar groove in rabbits. Soon after the procedure, a first subcutaneous injection of etanercept was performed. This single injection or, alternatively, 4 injections in total (twice a week for 2 weeks) were given. Each of these 2 groups was divided further into 3 subgroups: a low-dose group (0.05 microg/kg), an intermediate-dose group (0.4 microg/kg), and a high-dose group (1.6 microg /kg) with 19 rabbits in each. As a control, 19 rabbits were injected with water alone. The rabbits in each subgroup were killed 4 weeks (6 rabbits), 8 weeks (6 rabbits), or 24 weeks (7 rabbits) after surgery and repair was assessed histologically.
  
  
  RESULTS
  Histological examination revealed that the natural process of repair of the osteochondral defects was promoted by 4 subcutaneous injections of intermediate-dose etanercept and by 1 or 4 injections of high-dose etanercept at the various time points examined postoperatively (4, 8, and 24 weeks). Western blot showed that rabbit TNFalpha had a high affinity for etanercept.
  
  
  CONCLUSIONS
  Blocking of TNF by etanercept enabled repair of osteochondral defects in rabbit knee. Anti-TNF therapy could be a strategy for the use of tissue engineering for bone and cartilage repair.
authors.affiliation: Department of Orthopaedic Surgery, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: Amu
authors.initials: A
authors.lastname: Kawaguchi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nakaya
authors.forename: Takahiro
authors.initials: T
authors.lastname: Okabe
authors.forename: Keiji
authors.initials: K
authors.lastname: Tensho
authors.forename: Masashi
authors.initials: M
authors.lastname: Nawata
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Eguchi
authors.forename: Yuuki
authors.initials: Y
authors.lastname: Imai
authors.forename: Kunio
authors.initials: K
authors.lastname: Takaoka
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Wakitani
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage*; D015153:Blotting, Western; D002356:Cartilage / Q000187:drug effects / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D000068800:Etanercept; D007074:Immunoglobulin G / Q000008:administration & dosage*; D007279:Injections, Subcutaneous; D010007:Osteochondritis / Q000188:drug therapy* / Q000473:pathology; D010329:Patella / Q000187:drug effects* / Q000473:pathology; D011817:Rabbits; D018124:Receptors, Tumor Necrosis Factor / Q000008:administration & dosage*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000068800:Etanercept