CaSR, the calcium-sensing receptor, is a class-C G protein-coupled receptor. It plays a pivotal role in regulating calcium homeostasis by sensing small concentration changes of extracellular Ca2+, Mg2+, amino acids, small peptides, anions, and pH. CaSR-mediated intracellular Ca2+ signaling regulates diverse cellular processes such as gene transcription, cell proliferation, differentiation, apoptosis, muscle contraction, and neuronal transmission [1].

In conditional and global CaSR knockout mice, colonic epithelia show increased proliferation with enhanced Wnt/β-catenin signaling, indicating that CaSR negatively modulates colonic epithelial growth [2]. In Prg4-CreERT2 mice with CaSR or PTHrP gene deletion, mandibular condylar cartilage thickness is reduced, the proliferation and early differentiation of superficial zone cells are suppressed, and cartilage thickening and matrix production promoted by bilateral elevation bite are inhibited [3].

In conclusion, CaSR is crucial for maintaining calcium homeostasis and regulating various cellular processes. The study of CaSR knockout mouse models has provided insights into its role in colonic epithelial growth regulation and mandibular condylar cartilage development, contributing to our understanding of related physiological and disease processes.

References:

1. Tian, Li, Andrews, Corey, Yan, Qiuyun, Yang, Jenny J. 2024. Molecular regulation of calcium-sensing receptor (CaSR)-mediated signaling. In Chronic diseases and translational medicine, 10, 167-194. doi:10.1002/cdt3.123. https://pubmed.ncbi.nlm.nih.gov/39027195/

2. Macleod, R John. 2013. CaSR function in the intestine: Hormone secretion, electrolyte absorption and secretion, paracrine non-canonical Wnt signaling and colonic crypt cell proliferation. In Best practice & research. Clinical endocrinology & metabolism, 27, 385-402. doi:10.1016/j.beem.2013.05.005. https://pubmed.ncbi.nlm.nih.gov/23856267/

3. Zhou, Peng, Yang, Hongxu, Zhang, Mian, Liu, Jiguang, Wang, Meiqing. . CaSR modulates proliferation of the superficial zone cells in temporomandibular joint cartilage via the PTHrP nuclear localization sequence. In FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 37, e23004. doi:10.1096/fj.202300037RR. https://pubmed.ncbi.nlm.nih.gov/37440279/