A higher expression of P2X7 receptor at the site of heterotopic ossification promotes osteogenesis

Abstract Background Heterotopic ossification (HO) refers to a painful and complex disease. Adenosine triphosphate (ATP), as a key modulator of inflammation, is verified to promote the development of HO. However, the mechanism remains to be illustrated. The ionotropic P2X7 receptor (P2X7R) is an ATP-gated ion channel expressed in the majority of stem cells. Here, this paper hypothesizes that P2X7R may be activated by extracellular ATP and promote osteogenesis of stem cells under inflammatory condition, ending up in the formation of ectopic bone. Methods The tenotomy puncture and burn injury-induced HO model was constructed. The expression of P2X7R was found increasing at the site of injured Achilles tendon where HO occurs. Mesenchymal stem cells (MSCs) were cultivated under an inflammatory condition plus Bz-ATP treatment which mimicked a microenvironment of HO site. An induction in P2X7R expression was also observed along with an enhancement of osteogenesis. In addition, an inhibition of P2X7R expression by its specific antagonist successfully reversed the above process. Results P2X7R expression of the Achilles tendon and osteogenic capability of SCs is higher in HOG than in other two groups. Bz-ATP promoted osteogenesis under inflammation condition. BBG impeded the heterotopic bone formation in animal model. Conclusions P2X7R is a crucial mediator in ATP-signaling promotion of HO, blocking which may represent a potential therapeutic target for HO.