GLI1 and AXIN2 Are Distinctive Markers of Human Calvarial Mesenchymal Stromal Cells in Nonsyndromic Craniosynostosis
GLI1 and AXIN2 Are Distinctive Markers of Human Calvarial Mesenchymal Stromal Cells in Nonsyndromic Craniosynostosis
复制标题
DOI：
10.3390/ijms21124356
复制
发表时间：
2020-06-01
影响因子：
5.6
通讯作者：
Lattanzi, Wanda
中科院分区：
文献类型：
--
作者：
Di Pietro, Lorena;Barba, Marta;Lattanzi, Wanda
所有的骨骼都有成骨干细胞龛，其中间充质基质细胞（MSC）为组织生长和再生提供祖细胞。它们在通过软骨内骨化形成的长骨中被广泛研究。关于扁骨中成骨龛的组成的信息有限（即，通过直接的膜性骨化而形成。颅缝早闭症（CS）是一种先天性颅面缺损，由于过度和过早骨化的颅骨穹窿缝。本研究旨在分析GLI1，AXIN 2和THY 1在人类颅骨穹窿的表达，使用非综合征形式的CS（NCS）作为模型，以测试其在异常成骨过程中的功能意义。在NCS患者的颅骨样本中研究所选标志物的表达，以评估细胞的体内定位，并在其分离的MSC中研究所选标志物的表达。在体外成骨分化过程中分析标志物表达谱以验证功能意义。我们的结果表明，GLI 1和AXIN 2在人类颅骨成骨龛内的骨膜和骨内膜位置表达。它们的表达在分离自颅骨的MSC中高于分离自长骨的MSC，并且在成骨定型和分化后趋于降低。特别是，从过早融合的缝线中分离的细胞中AXIN2表达低于从NCS患者的未缝合缝线中分离的细胞。这表明AXIN2可以合理地代表在CS中发生的过早骨化过程中经历耗竭的干细胞群体的标志物。
All skeletal bones house osteogenic stem cell niches, in which mesenchymal stromal cells (MSC) provide progenitors for tissue growth and regeneration. They have been widely studied in long bones formed through endochondral ossification. Limited information is available on the composition of the osteogenic niche in flat bones (i.e., skull vault bones) that develop through direct membranous ossification. Craniosynostosis (CS) is a congenital craniofacial defect due to the excessive and premature ossification of skull vault sutures. This study aimed at analysing the expression of GLI1, AXIN2 and THY1 in the context of the human skull vault, using nonsyndromic forms of CS (NCS) as a model to test their functional implication in the aberrant osteogenic process. The expression of selected markers was studied in NCS patients' calvarial bone specimens, to assess the in vivo location of cells, and in MSC isolated thereof. The marker expression profile was analysed during in vitro osteogenic differentiation to validate the functional implication. Our results show that GLI1 and AXIN2 are expressed in periosteal and endosteal locations within the osteogenic niche of human calvarial bones. Their expression is higher in MSC isolated from calvarial bones than in those isolated from long bones and tends to decrease upon osteogenic commitment and differentiation. In particular, AXIN2 expression was lower in cells isolated from prematurely fused sutures than in those derived from patent sutures of NCS patients. This suggests that AXIN2 could reasonably represent a marker for the stem cell population that undergoes depletion during the premature ossification process occurring in CS.