Academy of Orthopedics, Guangdong Province, Department of Orthopedic Surgery, The Third Affiliated Hospital of Southern Medical University, Guangzhou 510630, China.
Department of Cell Biology, School of Basic Medical Science, Southern Medical University, Guangzhou 510515, China.
Biomed Res Int. 2020 Mar 26;2020:4572687. doi: 10.1155/2020/4572687. eCollection 2020.
TSC1-related signaling plays a pivotal role in intramembranous and endochondral ossification processes during skeletogenesis. This study was aimed at determining the significance of the TSC1 gene at different stages of spinal development. . TSC1-floxed mice (TSC1) were crossed with Prrx1-Cre or BGLAP-Cre transgenic mice or mesenchymal stem cell- and osteoblast-specific TSC1-deficient mice, respectively. Somatic and vertebral differences between WT and Prrx1-TSC1 null mice were examined at 4 weeks after birth.
No apparent body size abnormalities were apparent in newborn and 4-week- to 2-month-old mice with BGLAP-Cre driver-depleted TSC1. Vertebral and intervertebral discs displayed strong dysplasia in Prrx1-TSC1 null mice. In contrast, vertebrae were only slightly affected, and intervertebral discs from skeletal preparations displayed no apparent changes in BGLAP-TSC1 null mice.
Our data suggest that the TSC1 gene is crucial for endochondral ossification during postnatal spine development but plays discriminative roles at different stages. Mesenchymal stem cell-specific ablation of TSC1 led to severe spinal dysplasia at early stages of endochondral ossification while osteoblast-specific deletion of TSC1 affected vertebrae slightly and had no detectable effects on intervertebral discs.
TSC1 相关信号在骨骼发生过程中的膜内和软骨内成骨过程中发挥关键作用。本研究旨在确定 TSC1 基因在脊柱发育不同阶段的意义。分别将 TSC1 基因敲除（TSC1）小鼠与 Prrx1-Cre 或 BGLAP-Cre 转基因小鼠或骨髓间充质干细胞和成骨细胞特异性 TSC1 缺失小鼠杂交。在出生后 4 周时检查 WT 和 Prrx1-TSC1 缺失小鼠之间的躯体和椎骨差异。
在 BGLAP-Cre 驱动的 TSC1 缺失的新生和 4 周至 2 月龄小鼠中，未见明显的体型异常。Prrx1-TSC1 缺失小鼠的椎体和椎间盘表现出明显的发育不良。相比之下，BGLAP-TSC1 缺失小鼠的椎骨仅受到轻微影响，骨骼准备中的椎间盘也没有明显变化。
我们的数据表明，TSC1 基因对于出生后脊柱发育过程中的软骨内成骨至关重要，但在不同阶段发挥不同的作用。骨髓间充质干细胞特异性 TSC1 缺失导致软骨内成骨早期严重的脊柱发育不良，而成骨细胞特异性 TSC1 缺失对椎骨影响较小，对椎间盘没有可检测到的影响。
