Bone morphogenetic protein rescues the lack of secondary cartilage in Runx2-deficient mice
Bone morphogenetic protein rescues the lack of secondary cartilage in Runx2-deficient mice
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DOI：
10.1111/j.1469-7580.2007.00739.x
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发表时间：
2007-07-01
影响因子：
2.4
通讯作者：
Komori, Toshihisa
中科院分区：
文献类型：
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作者：
Fukuoka, Hiroki;Shibata, Shunichi;Komori, Toshihisa
包括髁突软骨在内的次级软骨具有独特的特征。它们起源于骨膜的碱性磷酸酶（ALP）阳性祖细胞，并表现出特征性的分化模式。它们还具有独特的细胞外基质，并共表达I型、II型和X型胶原。我们以前已经表明，在Runx 2缺陷（Runx 2-/-）小鼠中完全没有次级软骨。为了阐明Runx 2是否是软骨细胞分化的次级软骨，我们进行了器官培养系统，使用下颌外植体来自Runx 2-/-小鼠在胚胎第18.0天。由于骨形态发生蛋白2（BMP 2）的mRNA在野生型小鼠髁突原基的成骨细胞中强烈表达，而在Runx 2-/-小鼠中下调，我们选择研究BMP 2对次级软骨形成的影响。预培养外植体中下颌骨髁突原基凝聚的间充质细胞呈ALP阳性，并表达I型胶原和Sox 9。在与重组人（rh）BMP 2培养后，从间充质凝聚中出现了显示ALP活性并表达Sox 5、Sox 9以及I型和II型胶原的软骨细胞。该表达谱与小鼠次级软骨中软骨细胞的报道模式相当。然而，在外植体中未观察到软骨细胞肥大。这些发现表明，BMP 2部分挽救软骨细胞分化，但不是软骨细胞肥大的继发性软骨形成在Runx 2-/-小鼠。Runx 2是继发性软骨形成中软骨细胞肥大所必需的，并且很可能由髁突原基中的成骨细胞大量分泌的BMP 2有助于继发性软骨形成的早期过程。
Secondary cartilages including mandibular condylar cartilage have unique characteristics. They originate from alkaline phosphatase (ALP)-positive progenitor cells of the periosteum, and exhibit characteristic modes of differentiation. They also have a unique extracellular matrix, and coexpress type I, II and X collagens. We have previously shown that there is a total absence of secondary cartilages in Runx2-deficient (Runx2-/-) mice. To clarify whether Runx2 is essential for chondrocytic differentiation of secondary cartilages, we performed an organ culture system using mandibular explants derived from Runx2-/- mice at embryonic day 18.0. Since mRNA for bone morphogenetic protein 2 (BMP2) was strongly expressed in osteoblasts of condylar anlagen in wild-type mice, and was down-regulated in those of Runx2-/- mice, we chose to investigate BMP2 effects on secondary cartilage formation. Condensed mesenchymal cells of mandibular condylar anlagen in precultured explants were ALP-positive and expressed type I collagen and Sox9. After culture with recombinant human (rh) BMP2, chondrocytic cells showing ALP activity and expressing Sox5, Sox9, and type I and II collagens, appeared from mesenchymal condensation. This expression profile was comparable with the reported pattern of chondrocytes in mouse secondary cartilages. However, chondrocyte hypertrophy was not observed in the explants. These findings indicate that BMP2 partially rescued chondrocyte differentiation but not chondrocyte hypertrophy in secondary cartilage formation in Runx2-/- mice. Runx2 is required for chondrocyte hypertrophy in secondary cartilage formation, and it is likely that BMP2, which is abundantly secreted by osteoblasts in condylar anlagen, contributes to the early process of secondary cartilage formation.