Apoptosis in murine calvarial bone and suture development
Apoptosis in murine calvarial bone and suture development
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DOI：
10.1046/j.0909-8836.1999.eos107406.x
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发表时间：
1999-08-01
影响因子：
1.9
通讯作者：
Thesleff, I
中科院分区：
文献类型：
--
作者：
Rice, DPC;Kim, HJ;Thesleff, I
为了研究细胞凋亡在颅骨骨和缝合线发育中的可能作用，对 E14 至 P6 小鼠的颅骨整体和切片进行末端脱氧核苷酸转移酶介导的切口末端标记 (TUNEL)。我们还通过原位杂交分析了 Msx2、Bmp4 和 Bmp7 基因的表达，已知这些基因在导致细胞凋亡的保守信号通路中发挥作用。我们在颅骨、间缝和囟门中发现了从 E16 开始的 TUNEL 阳性细胞。 TUNEL 阳性成骨细胞和前成骨细胞在成骨前沿（成骨活性强的区域）或附近被鉴定，TUNEL 阳性间充质细胞位于缝间中充质。还观察到零星的 TUNEL 阳性破骨细胞和骨细胞，以及 TUNEL 阳性硬脑膜细胞。 Msx2 在缝间充质和硬脑膜中表达。 Bmp4 在发育中的骨、下面的硬脑膜、成骨前沿以及缝间充质中表达较弱。 Bmp7 在与 Bmp4 相同的位置被检测到，但在脑膜和表皮上的强度明显更强。我们认为这种细胞凋亡是正常缝线发育的一部分，并且是骨形成和骨吸收之间平衡不可或缺的一部分，因此异常细胞凋亡可能导致过早（颅缝早闭）或延迟（锁骨颅骨发育不良）缝线闭合。
To study the possible role of apoptosis in calvarial bone and suture development, terminal deoxynucleotidyl transferase-mediated nick-end labeling (TUNEL) was performed on whole mount and sectioned calvariae from mice aged between E14 and P6. We also analyzed by in situ hybridization the expression of Msx2, Bmp4 and Bmp7 genes, which are known to act in conserved signaling pathways leading to apoptosis. We found TUNEL-positive cells from E16 onwards in the calvarial bones, intervening sutures and fontanelles. TUNEL-positive osteoblasts and preosteoblasts were identified at or close to the osteogenic fronts, areas of intense osteogenic activity, with TUNEL-positive mesenchymal cells located in the midsutural mesenchyme. TUNEL-positive osteoclasts and osteocytes were also observed in a sporadic fashion, as well as TUNEL-positive dural cells. Msx2 was expressed in the sutural mesenchyme and the dura mater. Bmp4 was expressed in the developing bone, underlying dura mater, the osteogenic fronts, and also weakly in the sutural mesenchyme. Bmp7 was detected at the same locations as Bmp4 but with noticeably stronger intensity in the meninges and overlying epidermis. We propose that this apoptosis is part of normal suture development, and is integral to the balance between bone formation and resorption, so that abnormal apoptosis may lead to premature (Craniosynostosis) or delayed (Cleidocranial dysplasia) suture closure.