P2rx5, a member of the P2X family of ligand-gated cation channels, mediates signaling in response to extracellular ATP [2]. It is involved in multiple biological processes. P2rx5 is expressed in various cell types, including neurons, muscle cells, leukocytes, and adipocytes, and is associated with pathways related to cell activation, immunoregulation, and energy homeostasis [2,3]. Genetic models, such as knockout mice, are valuable for studying its function.

In a P2rx5 knockout male mouse model, loss of P2rx5 led to reduced brown adipocyte differentiation in vitro and browning in vivo. Agonism of P2RX5 exerted an anti-obesity effect in male mice housed at thermoneutrality with enhanced brown adipose tissue recruitment, suggesting its role in mediating brown adipocyte differentiation and function, which could be targeted for adipose tissue pathology and metabolic diseases [1]. In experimental periodontitis mouse models, P2rx5-/-mice showed decreased bone loss compared to wild-type and P2rx7-/-mice, with reduced expression of inflammatory cytokines like IL1b, IL6, IL17a, and Tnfsf11 in gingival tissue, indicating P2rx5 may regulate periodontitis-related bone loss [4].

In conclusion, P2rx5 is crucial for brown adipocyte differentiation and energy homeostasis, as well as for regulating bone loss in periodontitis, as revealed by knockout mouse models. Understanding P2rx5 function through these models provides potential therapeutic targets for metabolic diseases and periodontitis [1,4].

References:

1. Razzoli, Maria, McGonigle, Seth, Sahu, Bhavani Shankar, Frontini, Andrea, Bartolomucci, Alessandro. 2024. A key role for P2RX5 in brown adipocyte differentiation and energy homeostasis. In Adipocyte, 13, 2421745. doi:10.1080/21623945.2024.2421745. https://pubmed.ncbi.nlm.nih.gov/39484996/

2. Abramowski, Pierre, Ogrodowczyk, Christoph, Martin, Roland, Pongs, Olaf. 2014. A truncation variant of the cation channel P2RX5 is upregulated during T cell activation. In PloS one, 9, e104692. doi:10.1371/journal.pone.0104692. https://pubmed.ncbi.nlm.nih.gov/25181038/

3. Ussar, Siegfried, Lee, Kevin Y, Dankel, Simon N, Mellgren, Gunnar, Kahn, C Ronald. . ASC-1, PAT2, and P2RX5 are cell surface markers for white, beige, and brown adipocytes. In Science translational medicine, 6, 247ra103. doi:10.1126/scitranslmed.3008490. https://pubmed.ncbi.nlm.nih.gov/25080478/

4. Kim, Hyunsoo, Kajikawa, Tetsuhiro, Walsh, Matthew C, Hajishengallis, George, Choi, Yongwon. . The purinergic receptor P2X5 contributes to bone loss in experimental periodontitis. In BMB reports, 51, 468-473. doi:. https://pubmed.ncbi.nlm.nih.gov/30103845/