Extracellular ATP and its derivatives provide spatiotemporal guidance for bone adaptation to wide spectrum of physical forces

Chrisanne Dsouza; Mahmoud S Moussa; Nicholas Mikolajewicz; Svetlana V Komarova

doi:10.1016/j.bonr.2022.101608

Extracellular ATP and its derivatives provide spatiotemporal guidance for bone adaptation to wide spectrum of physical forces

Bone Rep. 2022 Aug 1:17:101608. doi: 10.1016/j.bonr.2022.101608. eCollection 2022 Dec.

Authors

Chrisanne Dsouza^{1

2}, Mahmoud S Moussa^{2

3}, Nicholas Mikolajewicz^{2

3}, Svetlana V Komarova^{1

2

3}

Affiliations

¹ Department of Experimental Surgery, McGill University, Montreal, QC H3G 1A4, Canada.
² Shriners Hospitals for Children- Canada, Montreal, QC H4A 0A9, Canada.
³ Faculty of Dental Medicine and Oral Health Sciences, McGill University, Montreal, QC H3A 1G1, Canada.

Abstract

ATP is a ubiquitous intracellular molecule critical for cellular bioenergetics. ATP is released in response to mechanical stimulation through vesicular release, small tears in cellular plasma membranes, or when cells are destroyed by traumatic forces. Extracellular ATP is degraded by ecto-ATPases to form ADP and eventually adenosine. ATP, ADP, and adenosine signal through purinergic receptors, including seven P2X ATP-gated cation channels, seven G-protein coupled P2Y receptors responsive to ATP and ADP, and four P1 receptors stimulated by adenosine. The goal of this review is to build a conceptual model of the role of different components of this complex system in coordinating cellular responses that are appropriate to the degree of mechanical stimulation, cell proximity to the location of mechanical injury, and time from the event. We propose that route and amount of ATP release depend on the scale of mechanical forces, ranging from vesicular release of small ATP boluses upon membrane deformation, to leakage of ATP through resealable plasma membrane tears, to spillage of cellular content due to destructive forces. Correspondingly, different P2 receptors responsive to ATP will be activated according to their affinity at the site of mechanical stimulation. ATP is a small molecule that readily diffuses through the environment, bringing the signal to the surrounding cells. ATP is also degraded to ADP which can stimulate a distinct set of P2 receptors. We propose that depending on the magnitude of mechanical forces and distance from the site of their application, ATP/ADP profiles will be different, allowing the relay of information about tissue level injury and proximity. Lastly, ADP is degraded to adenosine acting via its P1 receptors. The presence of large amounts of adenosine without ATP, indicates that an active source of ATP release is no longer present, initiating the transition to the recovery phase. This model consolidates the knowledge regarding the individual components of the purinergic system into a conceptual framework of choreographed responses to physical forces.

Keywords: ADA, Adenosine deaminase; ADK, Adenosine kinase; ADP; ADP, Adenosine diphosphate; ALP, Alkaline phosphatase; AMP, Adenosine monophosphate; AR, Adenosine receptor; ATP; ATP, Adenosine triphosphate; Adenosine; Bone; Cyto-5′NT, Cytosolic 5′ nucleotidase; ENTs, Equilibrative nucleoside transporter; Mechanobiology; NO, Nitric Oxide; NPP, Ecto-nucleotide pyrophosphatase/phosphodiesterases; NTPDases, Ecto-nucleoside triphosphate diphosphohydrolases; PG, Prostaglandins; PLC, Phospholipase C; PMD, Plasma membrane disruptions; Purinergic signaling; SAH, S-adenosyl-L-homocysteine; SNP, Single nucleotide polymorphism; TRAP, Tartrate resistant acid phosphatase; cAMP, Cyclic AMP; eN, Ecto-5′-nucleotidase.

Publication types

Review