Kusafuka Kimihide, Hiraki Yuji, Shukunami Chisa, Kayano Teruo, Takemura Tamiko
Department of Pathology, Japanese Red Cross Medical Center, Tokyo.
Acta Histochem. 2002;104(2):167-75. doi: 10.1078/0065-1281-00642.
Although cartilage contains many angiogenic factors during endochondral ossification, it is an avascular tissue. The cartilage-specific non-collagenous matrix protein chondromodulin-I (ChM-I) has been shown to be a strong angio-inhibitor. To elucidate whether ChM-I plays an essential role in angio-inhibition during endochondral ossification in man, we investigated the expression and localization of ChM-I in comparison with those of angiogenic factors and the endothelial cell marker CD34 in human neonatal vertebral tissues. Although invasion of CD34-positive endothelial cells was observed in primary subchondral spongiosa, expression of the marker of endothelial cells, CD34, was not found in neonatal vertebral cartilage matrix. Type II collagen was deposited in all matrices during endochondral ossification, whereas aggrecan was deposited in the matrix of hypertrophic cartilage, especially around lacunae. Vascular endothelial growth factor (VEGF), which is known to be a strong angiogenic factor, was localized in chondrocytes in mature to hypertrophic cartilage and also in bone marrow. Fibroblast growth factor-2 (FGF-2; basic fibroblast growth factor), which is also known to be a strong angiogenic factor, was localized in the cytoplasm of chondrocytes of mature cartilage in human vertebral cartilage tissues. Transforming growth factor (TGF)-beta has been reported to have many functions including angiogenesis, and TGF-beta1 was also localized in mature chondrocytes in endochondral tissues undergoing ossification. On the other hand, the novel cartilage-specific matrix protein ChM-I was localized in interterritorial regions of the matrix in mature to hypertrophic cartilage, especially around lacunae. In conclusion, these observations indicate that ChM-I may serve as a barrier against the angiogenic properties of VEGF, FGF-2 and TGF-beta1 during endochondral ossification, and this matrix molecule may play an essential role in determining the avascular nature of cartilage in vivo.
尽管软骨在软骨内成骨过程中含有许多血管生成因子，但它是一种无血管组织。软骨特异性非胶原蛋白基质蛋白软骨调节素-I（ChM-I）已被证明是一种强大的血管生成抑制剂。为了阐明ChM-I在人类软骨内成骨过程中的血管生成抑制中是否起关键作用，我们研究了ChM-I与血管生成因子和内皮细胞标志物CD34在人类新生儿椎体组织中的表达及定位。尽管在初级软骨下松质骨中观察到CD34阳性内皮细胞的侵入，但在新生儿椎体软骨基质中未发现内皮细胞标志物CD34的表达。II型胶原蛋白在软骨内成骨过程中沉积于所有基质中，而聚集蛋白聚糖则沉积于肥大软骨的基质中，尤其是在陷窝周围。血管内皮生长因子（VEGF）是一种已知的强大血管生成因子，定位于成熟至肥大软骨的软骨细胞以及骨髓中。成纤维细胞生长因子-2（FGF-2；碱性成纤维细胞生长因子）也是一种已知的强大血管生成因子，定位于人类椎体软骨组织中成熟软骨的软骨细胞胞质内。据报道，转化生长因子（TGF）-β具有包括血管生成在内的多种功能；TGF-β1也定位于正在进行骨化的软骨内组织的成熟软骨细胞中。另一方面，新型软骨特异性基质蛋白ChM-I定位于成熟至肥大软骨基质的区域间，尤其是在陷窝周围。总之，这些观察结果表明，ChM-I可能在软骨内成骨过程中作为VEGF、FGF-2和TGF-β1血管生成特性的屏障，并且这种基质分子可能在决定体内软骨的无血管性质中起关键作用。
