Cranial Base Synchondrosis Lacks PTHrP-Expressing Column-Forming Chondrocytes.

Cranial Base Synchondrosis Lacks PTHrP-Expressing Column-Forming Chondrocytes.
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DOI:
10.3390/ijms23147873
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发表时间:
2022-07-17
影响因子:
5.6
通讯作者:
--
中科院分区:
生物学2区
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颅底包含一种特殊类型的生长板,称为软骨联合,其功能是颅骨的生长中心。软骨联合由静止、增殖和肥大软骨细胞的双向相对层组成,并且缺乏次级骨化中心。在长骨中,骨骺生长板的休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。软骨联合中的 PTHrP+ 软骨细胞是否具有相似的功能仍不清楚。使用 Pthrp-mCherry 敲入小鼠,我们发现 PTHrP+ 软骨细胞主要占据软骨联合的外侧楔形区域,这与位于骨骺内休息区的股骨生长板中的软骨细胞不同。使用他莫昔芬诱导的 Pthrp-creER 系进行的体内细胞谱系分析表明,PTHrP+ 软骨细胞未能在软骨联合中建立柱状软骨细胞。因此,与长骨生长板静止区中的​​软骨细胞不同,软骨联合中的 PTHrP+ 软骨细胞不具备柱形成能力。这些发现支持长骨骨骺内的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,其缺乏可能解释颅底联合软骨中 PTHrP+ 软骨细胞缺乏柱形成能力。
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.
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