Interleukin-1 and tumor necrosis factor alpha inhibit repair of the porcine meniscus in vitro.
OBJECTIVE
Injury or removal of the knee meniscus leads to progressive joint degeneration, and current surgical therapies for meniscal tears seek to maximally preserve meniscal structure and function. However, the factors that influence intrinsic repair of the meniscus are not well understood. The goal of this study was to investigate the capacity of meniscus tissue to repair a simulated defect in vitro and to examine the effect of pro-inflammatory cytokines on this process.


METHODS
Cylindrical explants were harvested from the outer one-third of medial porcine menisci. To simulate a full-thickness defect, a central core was removed and reinserted immediately into the defect. Explants were cultured for 2, 4, or 6 weeks in serum-containing media in the presence or absence of interleukin-1 (IL-1) or tumor necrosis factor alpha (TNF-alpha), and meniscal repair was investigated using mechanical testing and fluorescence confocal microscopy.


RESULTS
Meniscal lesions in untreated samples showed a significant capacity for intrinsic repair in vitro, with increasing cell accumulation and repair strength over time in culture. In the presence of IL-1 or TNF-alpha, no repair was observed despite the presence of abundant viable cells.


CONCLUSIONS
This study demonstrates that the meniscus exhibits an intrinsic repair response in vitro. However, the presence of pro-inflammatory cytokines completely inhibited repair. These findings suggest that increased levels of pro-inflammatory cytokines post-injury or under arthritic conditions may inhibit meniscal repair. Therefore, inhibition of these cytokines may provide a means of accelerating repair of damaged or injured menisci in vivo.
Hennerbichler
A
A
Department of Surgery, Division of Orthopaedic Surgery, Duke University Medical Center, Durham, NC 27710, USA.
Moutos
F T
FT
Hennerbichler
D
D
Weinberg
J B
JB
Guilak
F
F
D000818:Animals; D002470:Cell Survival; D005453:Fluorescence; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000494:pharmacology*; D008592:Menisci, Tibial / Q000166:cytology* / Q000502:physiology*; D018613:Microscopy, Confocal; D013314:Stress, Mechanical; D013552:Swine; D000070600:Tibial Meniscus Injuries; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D014945:Wound Healing / Q000187:drug effects
D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha