Blocking of tumor necrosis factor activity promotes natural repair of osteochondral defects in rabbit knee.
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.
Kawaguchi
Amu
A
Department of Orthopaedic Surgery, Shinshu University School of Medicine, Matsumoto, Japan.
Nakaya
Hiroyuki
H
Okabe
Takahiro
T
Tensho
Keiji
K
Nawata
Masashi
M
Eguchi
Yoshitaka
Y
Imai
Yuuki
Y
Takaoka
Kunio
K
Wakitani
Shigeyuki
S
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
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000068800:Etanercept