Shibata Shunichi, Baba Otto, Oda Tsuyoshi, Yokohama-Tamaki Tamaki, Qin Chunlin, Butler William T, Sakakura Yasunori, Takano Yoshiro
Division of Histology, Department of Oral Growth and Development, School of Dentistry, Health Sciences University of Hokkaido, 1757 Kanazawa, Tobetsu-cho, Ishikari-gun, Hokkaido, Japan.
Arch Oral Biol. 2008 Mar;53(3):220-30. doi: 10.1016/j.archoralbio.2007.10.010. Epub 2007 Dec 19.
Previous studies indicate that hypertrophic chondrocytes can transdifferentiate or dedifferentiate and redifferentiate into bone cells during the endochondral bone formation. Mandibular condyle in aged c-src-deficient mice has incremental line-like striations consisting of cartilaginous and non-cartilaginous layers, and the former contains intact hypertrophic chondrocytes in uneroded lacunae. The purpose of this study is to determine the phenotype changes of uneroded hypertrophic chondrocytes.
Immunohistochemical and ultrastructural examinations of the pericellular matrix of hypertrophic chondrocytes in the upper, middle, and lower regions of the mandibular condyle were conducted in aged c-src-deficient mice, using several antibodies of cartilage/bone marker proteins.
Co-localisation of aggrecan, type I collagen, and dentin matrix protein-1 (DMP-1) or matrix extracellular phosphoprotein (MEPE) was detected in the pericellular matrix of the middle region. Ultrastructurally, granular substances in the pericellular matrix of the middle region were the remains of upper region chondrocytes, which were mixed with thick collagen fibrils. In the lower region, the width of the pericellular matrix and the amount of collagen fibrils were increased. Versican, type I collagen, DMP-1, and MEPE were detected in the osteocyte lacunae. Additionally, DMP-1 and MEPE were detected in the pericellular matrix of uneroded hypertrophic chondrocytes located in the lower, peripheral region of the mandibular condyle in younger c-src-deficient mice, but not in the aged wild-type mice.
These results indicate that long-term survived, uneroded hypertrophic chondrocytes, at least in a part, acquire osteocytic characteristics.
先前的研究表明,在软骨内骨形成过程中,肥大软骨细胞可转分化或去分化并重新分化为骨细胞。老年c-src基因缺陷小鼠的下颌髁突有由软骨层和非软骨层组成的递增线状条纹,前者在未侵蚀的陷窝中含有完整的肥大软骨细胞。本研究的目的是确定未侵蚀的肥大软骨细胞的表型变化。
使用几种软骨/骨标记蛋白抗体,对老年c-src基因缺陷小鼠下颌髁突上、中、下区域肥大软骨细胞的细胞周基质进行免疫组织化学和超微结构检查。
在中间区域的细胞周基质中检测到聚集蛋白聚糖、I型胶原蛋白和牙本质基质蛋白-1(DMP-1)或基质细胞外磷酸化蛋白(MEPE)的共定位。超微结构上,中间区域细胞周基质中的颗粒物质是上部区域软骨细胞的残余物,与粗大的胶原纤维混合在一起。在下部区域,细胞周基质的宽度和胶原纤维的数量增加。在骨细胞陷窝中检测到多功能蛋白聚糖、I型胶原蛋白、DMP-1和MEPE。此外,在年轻的c-src基因缺陷小鼠下颌髁突下部周边区域未侵蚀的肥大软骨细胞的细胞周基质中检测到DMP-1和MEPE,但在老年野生型小鼠中未检测到。
这些结果表明,长期存活、未侵蚀的肥大软骨细胞至少部分获得了骨细胞特征。