Pth1r, the type 1 parathyroid hormone receptor, is a G protein-coupled receptor crucial for mineral ion homeostasis and bone metabolism. It is activated by parathyroid hormone (PTH) and PTH-related protein (PTHrP), triggering the cAMP/protein kinase A (PKA) pathway [1]. Pth1r signaling also plays a role in the regulation of osteoclast formation via osteoblast lineage cells [1].

In multiple mouse models, significant findings have emerged. Gli1-CreERT2;Pth1rfl/fl;Tomatofl/+ mice showed that Pth1r signaling in Gli1-positive cells is essential for postnatal development and maintenance of cranial base synchondroses, as mutants had shortened cranial bases and premature synchondrosis closure [2]. Wnt1-Cre;Pth1rfl/fl;Tomatofl/+ mice had perinatal lethality, along with craniofacial defects like short snouts, jaws, and abnormal nasal cartilage differentiation [3]. Prx1Cre;PTH1Rfl/fl mice had decreased alveolar bone mass due to apoptotic response activation in Prx1-positive mesenchymal cells [5]. Deleting Kindlin-2 in osteoblastic cells using 10-kb Dmp1-Cre in mice largely neutralized intermittent PTH-stimulated increases in bone volume fraction and density, suggesting Kindlin-2 modulates PTH1R in regulating skeletal homeostasis [4].

In conclusion, Pth1r is vital for bone-related biological processes and development. The gene knockout and conditional knockout mouse models have significantly contributed to understanding its role in cranial base development, nasal cartilage differentiation, mandibular growth, and skeletal homeostasis, providing insights into potential mechanisms underlying related diseases [2,3,4,5].