P2rx7, the gene encoding the P2X7 receptor, is a non-selective ligand-gated homotrimeric cation channel. It functions as a danger sensor, detecting extracellular nucleotides from injured cells and triggering an inflammatory cascade. P2rx7 is expressed in immune cells and plays important roles in pathogen surveillance, cell-mediated responses to infectious organisms, and in various physiological and pathological processes such as pain, CNS and psychiatric disorders, and cancer [1,2].

In chronic nonbacterial osteomyelitis (CNO), rare presumably damaging P2rx7 variants were identified in patients. Patient-derived monocytes and genetically modified THP-1 cells with these variants showed altered potassium flux, inflammasome assembly, pyroptosis, and cytokine release, indicating that P2rx7 variants may be a CNO risk factor [3]. In osteosarcoma, P2rx7 knockout cell lines demonstrated that P2rx7 promotes glucose metabolism and osteosarcoma progression by enhancing c-Myc stabilization, suggesting it could be a potential diagnostic and therapeutic target [4].

In conclusion, P2rx7 is crucial in pathogen-host interactions, inflammation, and disease-related processes. Studies using gene knockout models in mice, like the P2rx7 knockout cell lines and analysis of P2rx7 variants in CNO patients, have revealed its role in specific disease conditions such as CNO and osteosarcoma, providing insights into potential therapeutic strategies for these diseases.

References:

1. Soare, Alexandra Y, Freeman, Tracey L, Min, Alice K, Osota, Elizabeth O, Swartz, Talia H. 2021. P2RX7 at the Host-Pathogen Interface of Infectious Diseases. In Microbiology and molecular biology reviews : MMBR, 85, . doi:10.1128/MMBR.00055-20. https://pubmed.ncbi.nlm.nih.gov/33441488/

2. Young, Chris N J, Górecki, Dariusz C. 2018. P2RX7 Purinoceptor as a Therapeutic Target-The Second Coming? In Frontiers in chemistry, 6, 248. doi:10.3389/fchem.2018.00248. https://pubmed.ncbi.nlm.nih.gov/30003075/

3. Charras, Amandine, Hofmann, Sigrun R, Cox, Allison, Ferguson, Polly J, Hedrich, Christian M. 2024. P2RX7 gene variants associate with altered inflammasome assembly and reduced pyroptosis in chronic nonbacterial osteomyelitis (CNO). In Journal of autoimmunity, 144, 103183. doi:10.1016/j.jaut.2024.103183. https://pubmed.ncbi.nlm.nih.gov/38401466/

4. Sheng, Gaohong, Gao, Yuan, Ding, Qing, Wu, Hua, Yang, Yong. 2023. P2RX7 promotes osteosarcoma progression and glucose metabolism by enhancing c-Myc stabilization. In Journal of translational medicine, 21, 132. doi:10.1186/s12967-023-03985-z. https://pubmed.ncbi.nlm.nih.gov/36803784/