Abstract:
The cranial base contains a special type of growth plate termed the synchondrosis, which functions as the growth center of the skull. The synchondrosis is composed of bidirectional opposite-facing layers of resting, proliferating, and hypertrophic chondrocytes, and lacks the secondary ossification center. In long bones, the resting zone of the epiphyseal growth plate houses a population of parathyroid hormone-related protein (PTHrP)-expressing chondrocytes that contribute to the formation of columnar chondrocytes. Whether PTHrP+ chondrocytes in the synchondrosis possess similar functions remains undefined. Using Pthrp-mCherry knock-in mice, we found that PTHrP+ chondrocytes predominantly occupied the lateral wedge-shaped area of the synchondrosis, unlike those in the femoral growth plate that reside in the resting zone within the epiphysis. In vivo cell-lineage analyses using a tamoxifen-inducible Pthrp-creER line revealed that PTHrP+ chondrocytes failed to establish columnar chondrocytes in the synchondrosis. Therefore, PTHrP+ chondrocytes in the synchondrosis do not possess column-forming capabilities, unlike those in the resting zone of the long bone growth plate. These findings support the importance of the secondary ossification center within the long bone epiphysis in establishing the stem cell niche for PTHrP+ chondrocytes, the absence of which may explain the lack of column-forming capabilities of PTHrP+ chondrocytes in the cranial base synchondrosis.
摘要:
颅底包含一种特殊类型的生长板,称为联合软骨症,作为头骨的生长中心。关节综合征由双向相对的静息层组成,增殖,和肥大的软骨细胞,缺乏次要骨化中心。在长骨中,骨phy生长板的静息区容纳了一群表达甲状旁腺激素相关蛋白(PTHrP)的软骨细胞,这些软骨细胞有助于柱状软骨细胞的形成。是否PTHrP+软骨细胞在联合软骨中具有相似的功能仍未确定。使用Pthrp-mCherry敲入小鼠,我们发现PTHrP+软骨细胞主要占据了软骨复合体的外侧楔形区域,与股骨生长板中位于骨phy静息区的股骨生长板中的那些不同。使用他莫昔芬诱导的Pthrp-creER品系进行的体内细胞系分析显示,PTHrP软骨细胞未能在软骨复合体中建立柱状软骨细胞。因此,PTHrP+软骨细胞在联合软骨不具备柱形成能力,与长骨生长板的静止区不同。这些发现支持了长骨骨phy中次级骨化中心在建立PTHrP软骨细胞干细胞生态位中的重要性,缺乏这些可能解释了PTHrP+软骨细胞在颅底软骨联合中缺乏柱形成能力。