IADR Abstract Archives
Characterization of PTHrP-expressing Resting Chondrocytes in the Spheno-Occipital Synchondrosis
Objectives: The cranial base contains bidirectional growth plates termed the synchondroses, which act as signaling centers that facilitate postnatal craniofacial growth through endochondral ossification. We identified a stem cell niche in the resting zone of the postnatal epiphyseal growth plate, in which PTHrP+ chondrocytes behave as skeletal stem cells. Due to the overlapping nature of the long bone and cranial base, we aim to elucidate the characteristics of PTHrP-expressing chondrocytes in the synchondrosis and how they maintain their growth potential.
Methods: We analyzed PTHrP expression in the spheno-occipital synchondrosis (SOS) at various stages of postnatal development using Pthrp-mCherry reporter mice. These mice also received EdU to evaluate cell proliferation. Additionally, we utilized a tamoxifen-inducible PTHrP-creER line to assess cell fates of PTHrP+ chondrocytes in the SOS and define if these cells contribute to formation of columnar chondrocytes.
Results: The hierarchical structure of the SOS was clearly established by P3. PTHrP+ chondrocytes appeared in a wedge-shaped area on the lateral borders of the SOS by P6. PTHrP+ cells were sparsely marked by EdU, indicating the slow-cycling nature of these cells. Cells in the central portion of the presumptive resting zone lacked PTHrP expression and possessed morphologies similar to hypertrophic chondrocytes. Lineage-tracing studies demonstrated that PTHrP+ chondrocytes did not robustly contribute to formation of columnar chondrocytes by becoming proliferating and hypertrophic chondrocytes.
Conclusions: We uncovered a novel paradigm of postnatal synchondrosis development using two PTHrP mouse models. Unlike in the epiphyseal growth plate, PTHrP+ cells are predominantly located in a wedge-shaped area on the lateral edge of the synchondrosis, and do not actively contribute to formation of columnar chondrocytes. Despite similar tissue organization, functions of the resting zone are likely to be vastly different between the epiphyseal growth plate and synchondrosis, requiring further investigation.
Methods: We analyzed PTHrP expression in the spheno-occipital synchondrosis (SOS) at various stages of postnatal development using Pthrp-mCherry reporter mice. These mice also received EdU to evaluate cell proliferation. Additionally, we utilized a tamoxifen-inducible PTHrP-creER line to assess cell fates of PTHrP+ chondrocytes in the SOS and define if these cells contribute to formation of columnar chondrocytes.
Results: The hierarchical structure of the SOS was clearly established by P3. PTHrP+ chondrocytes appeared in a wedge-shaped area on the lateral borders of the SOS by P6. PTHrP+ cells were sparsely marked by EdU, indicating the slow-cycling nature of these cells. Cells in the central portion of the presumptive resting zone lacked PTHrP expression and possessed morphologies similar to hypertrophic chondrocytes. Lineage-tracing studies demonstrated that PTHrP+ chondrocytes did not robustly contribute to formation of columnar chondrocytes by becoming proliferating and hypertrophic chondrocytes.
Conclusions: We uncovered a novel paradigm of postnatal synchondrosis development using two PTHrP mouse models. Unlike in the epiphyseal growth plate, PTHrP+ cells are predominantly located in a wedge-shaped area on the lateral edge of the synchondrosis, and do not actively contribute to formation of columnar chondrocytes. Despite similar tissue organization, functions of the resting zone are likely to be vastly different between the epiphyseal growth plate and synchondrosis, requiring further investigation.
