The distribution of vascular endothelial growth factor in human meniscus and a meniscal injury model.
BACKGROUND
The meniscus plays an important role in controlling the complex biomechanics of the knee. Meniscus injury is common in the knee joint. The perimeniscal capillary plexus supplies the outer meniscus, whereas the inner meniscus is composed of avascular tissue. Angiogenesis factors, such as vascular endothelial growth factor (VEGF), have important roles in promoting vascularization of various tissues. VEGF-mediated neovascularization is beneficial to the healing of injured tissues. However, the distribution and angiogenic role of VEGF remains unclear in the meniscus and injured meniscus. We hypothesized that VEGF could affect meniscus cells and modulate the meniscus healing process.


METHODS
Menisci were obtained from total knee arthroplasty patients. Meniscal injury was created ex vivo by a microsurgical blade. VEGF mRNA and protein expression were detected by the polymerase chain reaction and immunohistochemical analyses, respectively.


RESULTS
In native meniscal tissue, the expression of VEGF and HIF-1α mRNAs could not be detected. However, VEGF and HIF-1α mRNAs were found in cultured meniscal cells (VEGF: outer > inner; HIF-1α: outer = inner). Injury increased mRNA levels of both VEGF and HIF-1α, with the increase being greatest in the outer area. Immunohistochemical analyses revealed that VEGF protein was detected mainly in the outer region and around injured areas of the meniscus. However, VEGF concentrations were similar between inner and outer menisci-derived media.


CONCLUSIONS
This study demonstrated that both the inner and outer regions of the meniscus contained VEGF. HIF-1α expression and VEGF deposition were high in injured meniscal tissue. Our results suggest that injury stimulates the expression of HIF-1α and VEGF that may be preserved in the extracellular matrix as the healing stimulator of damaged meniscus, especially in the outer meniscus.
Department of Orthopaedic Surgery, Okayama University Graduate School, 2-5-1 Shikatacho, Kitaku, Okayama 700-8558, Japan.
Zhichao
Z
Lu
Department of Orthopaedic Surgery, Okayama University Graduate School, 2-5-1 Shikatacho, Kitaku, Okayama 700-8558, Japan. Electronic address: matino@md.okayama-u.ac.jp.
Takayuki
T
Furumatsu
Department of Orthopaedic Surgery, Okayama University Graduate School, 2-5-1 Shikatacho, Kitaku, Okayama 700-8558, Japan.
Masataka
M
Fujii
Department of Orthopaedic Surgery, Okayama University Graduate School, 2-5-1 Shikatacho, Kitaku, Okayama 700-8558, Japan.
Ami
A
Maehara
Department of Orthopaedic Surgery, Okayama University Graduate School, 2-5-1 Shikatacho, Kitaku, Okayama 700-8558, Japan.
Toshifumi
T
Ozaki
D000368:Aged; D019645:Arthroplasty, Replacement, Knee; D005260:Female; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism*; D020370:Osteoarthritis, Knee / Q000378:metabolism / Q000601:surgery; D012333:RNA, Messenger / Q000378:metabolism; D000070600:Tibial Meniscus Injuries / Q000209:etiology / Q000378:metabolism*; D046509:Tissue Culture Techniques; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*
D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A