Localization and inhibitory effect of basic fibroblast growth factor on chondrogenesis in cultured mouse mandibular condyle
Localization and inhibitory effect of basic fibroblast growth factor on chondrogenesis in cultured mouse mandibular condyle
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DOI：
10.1007/s007740300023
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发表时间：
2003-01-01
影响因子：
3.3
通讯作者：
Kuroda, T
中科院分区：
文献类型：
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作者：
Ogawa, T;Shimokawa, H;Kuroda, T
髁突软骨是下颌骨的一个重要生长部位，具有独特的生长和分化模式，与肢芽软骨不同。为探讨髁突软骨发生的机制，采用无血清器官培养法，观察了碱性成纤维细胞生长因子（bFGF）对小鼠髁突生长发育的影响，以及对髁突软骨发生相关基因表达的影响。进一步用免疫组织化学方法观察bFGF在髁突中的定位。目前的免疫组化观察表明，碱性成纤维细胞生长因子是本地化的间充质髁状突原基，软骨膜和增殖细胞区的细胞外基质中，和异染染色区的免疫染色减少。在髁突培养中加入重组人bFGF（rhbFGF）5天后，肥大软骨细胞在髁突软骨中所占面积减少。逆转录-聚合酶链反应（RT-PCR）检测也表明，与未处理的组织相比，聚集蛋白聚糖和X型胶原的mRNA水平降低。用rhbFGF治疗2天可降低软骨膜中的细胞增殖，并且bFGF在RT-PCR测定中下调了印度刺猬（Ihh）、甲状旁腺相关蛋白（PTHrP）、骨形态发生蛋白4（BMP 4）和核心结合因子α 1（Cbfa 1）的表达。这些结果表明，碱性成纤维细胞生长因子具有抑制性调节髁突生长的能力，通过抑制软骨细胞的增殖和分化，并且这种抑制性调节与下调生长因子和转录因子有关。
The condylar cartilage, an important growth site in the mandible, shows characteristic modes of growth and differentiation, unlike the limb bud cartilage. To elucidate the mechanism of chondrogenesis at the condylar cartilage, we analyzed the effects of basic fibroblast growth factor (bFGF) on the growth and development of mouse mandibular condyle using serum-free organ culture and on the expression of genes related to the chondrogenesis. Further, we investigated the localization of bFGF in cultured condyle by immunohistochemistry. The present immunohistochemical observations showed that bFGF is localized in the extracellular matrix of the mesenchymal condylar anlage, the perichondrium and the proliferative cell zone, and that immunostaining was diminished in the metachromatically stained area. In the condyle culture with added recombinant human bFGF (rhbFGF) for 5 days, the area occupied by hypertrophic chondrocytes in the mandibular condylar cartilage was reduced. A reverse transcription-polymerase chain reaction (RT-PCR) assay also showed that the mRNA levels of aggrecan and type X collagen were reduced compared with nontreated tissues. Treatment with rhbFGF for 2 days decreased cell proliferation in the perichondrium, and bFGF downregulated the Indian hedgehog (Ihh), parathyroid hormone-related protein (PTHrP), bone morphogenetic protein 4 (BMP4), and core-binding factor alpha1 (Cbfa1) expression in the RT-PCR assay. These findings suggest that bFGF has the ability for inhibitory regulation of condylar growth, via the inhibition of proliferation and differentiation of chondrocytes, and that this inhibitory regulation is related to the downregulation of growth factors and transcription factors.