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Real-time Live-cell Flow Cytometry to Investigate Calcium Influx, Pore Formation, and Phagocytosis by P2X7 Receptors in Adult Neural Progenitor Cells
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ATP-P2X7R-NLRP3 Axis as a Unifying Mechanism of ATP-Induced Cell Death in Degenerative Bone and Cardiovascular

Jingjing Zhang1,2,3, Linzhu Li4, Qianwen Guo5

  • 1Fuwai Yunnan Hospital, Chinese Academy of Medical Sciences, Affiliated Cardiovascular Hospital of Kunming Medical University, Kunming, 650000, People's Republic of China.

Journal of Inflammation Research
|March 18, 2026
PubMed

Insights

Extracellular adenosine triphosphate (ATP) triggers cell death pathways common to degenerative bone diseases and cardiovascular diseases. Targeting the ATP-P2X7-NLRP3 axis offers integrated therapeutic strategies for these conditions.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Pathology

Background:

  • Extracellular adenosine triphosphate (ATP) functions as an energy signal and damage-associated molecular pattern (DAMP).
  • ATP is critically involved in the progression of degenerative bone diseases (DBD) and cardiovascular diseases (CVD).
  • Purinergic receptor activation, especially P2X7, by ATP initiates detrimental cellular events.

Purpose of the Study:

  • To elucidate the molecular mechanisms of ATP-induced cell death (AICD) in DBD and CVD.
  • To evaluate experimental and clinical evidence linking AICD to these diseases.
  • To discuss therapeutic strategies targeting the ATP-purinergic-mitochondrial axis for integrated treatment.

Main Methods:

  • Review of literature on molecular pathways of AICD.
  • Analysis of the role of the ATP-P2X7-NLRP3 axis.
  • Examination of cellular events including calcium influx, mitochondrial dysfunction, oxidative stress, and inflammasome activation.

Main Results:

  • AICD involves pyroptosis, apoptosis, and ferroptosis, contributing to osteoarthritis, disc degeneration, osteoporosis, myocardial infarction, and heart failure.
  • The ATP-P2X7-NLRP3 axis is a shared molecular mechanism in DBD and CVD.
  • Energy imbalance and chronic inflammation drive these pathological processes.

Conclusions:

  • The ATP-purinergic-mitochondrial axis is a key player in both degenerative bone and cardiovascular diseases.
  • Targeting this axis presents a promising avenue for developing integrated therapeutic approaches.
  • Understanding AICD mechanisms provides insights into treating complex, interconnected diseases.
Keywords:
ATP-induced cell deathNLRP3 inflammasomeP2X7 receptorcardiovascular remodelingdegenerative bone disordersmitochondrial dysfunctionpurinergic signaling

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