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Treatment of Osteochondral Defects in the Rabbit's Knee Joint by Implantation of Allogeneic Mesenchymal Stem Cells in Fibrin Clots
Published on: May 21, 2013
Blocking of tumor necrosis factor activity promotes natural repair of osteochondral defects in rabbit knee
Amu Kawaguchi1, Hiroyuki Nakaya, Takahiro Okabe
1Department of Orthopaedic Surgery, Shinshu University School of Medicine, Matsumoto, Japan.
Background And Purpose:
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.
Material And 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.
Interpretation:
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.
Insights
Blocking tumor necrosis factor (TNF) with etanercept promoted osteochondral defect repair in rabbits. This anti-TNF therapy shows promise for tissue engineering in bone and cartilage repair.
Area of Science:
- Orthopedics
- Regenerative Medicine
- Immunology
Background:
- Osteochondral defects have limited natural repair capacity.
- Tumor necrosis factor (TNF) plays a role in inflammatory processes affecting tissue repair.
Purpose of the Study:
- To investigate the effect of etanercept, a TNF signal blocker, on the repair of osteochondral defects in a rabbit knee model.
- To assess the efficacy of different etanercept dosages and administration frequencies.
Main Methods:
- Osteochondral defects were surgically created in rabbit knees.
- Rabbits received single or multiple subcutaneous injections of etanercept at varying doses (0.05, 0.4, 1.6 microg/kg) or a water control.
- Histological analysis was performed at 4, 8, and 24 weeks post-surgery.
Main Results:
- Histological examination showed enhanced repair of osteochondral defects with intermediate and high doses of etanercept.
- Four injections of intermediate-dose and one or four injections of high-dose etanercept promoted repair at all time points.
- Western blot confirmed high affinity between rabbit TNFalpha and etanercept.
Conclusions:
- Blocking TNF with etanercept facilitates the repair of osteochondral defects in rabbits.
- Anti-TNF therapy presents a potential strategy for bone and cartilage tissue engineering applications.

