Mechanically stimulated ATP release from murine bone cells is regulated by a balance of injury and repair
Bone cells sense and actively adapt to physical perturbations to prevent critical damage. ATP release is among the earliest cellular responses to mechanical stimulation. Mechanical stimulation of a single murine osteoblast led to the release of 70 ± 24 amole ATP, which stimulated calcium responses i...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2018-10-01
|
| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/37812 |
| _version_ | 1811199360524877824 |
|---|---|
| author | Nicholas Mikolajewicz Elizabeth A Zimmermann Bettina M Willie Svetlana V Komarova |
| author_facet | Nicholas Mikolajewicz Elizabeth A Zimmermann Bettina M Willie Svetlana V Komarova |
| author_sort | Nicholas Mikolajewicz |
| collection | DOAJ |
| description | Bone cells sense and actively adapt to physical perturbations to prevent critical damage. ATP release is among the earliest cellular responses to mechanical stimulation. Mechanical stimulation of a single murine osteoblast led to the release of 70 ± 24 amole ATP, which stimulated calcium responses in neighboring cells. Osteoblasts contained ATP-rich vesicles that were released upon mechanical stimulation. Surprisingly, interventions that promoted vesicular release reduced ATP release, while inhibitors of vesicular release potentiated ATP release. Searching for an alternative ATP release route, we found that mechanical stresses induced reversible cell membrane injury in vitro and in vivo. Ca2+/PLC/PKC-dependent vesicular exocytosis facilitated membrane repair, thereby minimizing cell injury and reducing ATP release. Priming cellular repair machinery prior to mechanical stimulation reduced subsequent membrane injury and ATP release, linking cellular mechanosensitivity to prior mechanical exposure. Thus, our findings position ATP release as an integrated readout of membrane injury and repair. |
| first_indexed | 2024-04-12T01:46:51Z |
| format | Article |
| id | doaj.art-186c84c71a1246caba150e4e7f6a9646 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T01:46:51Z |
| publishDate | 2018-10-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-186c84c71a1246caba150e4e7f6a96462022-12-22T03:53:02ZengeLife Sciences Publications LtdeLife2050-084X2018-10-01710.7554/eLife.37812Mechanically stimulated ATP release from murine bone cells is regulated by a balance of injury and repairNicholas Mikolajewicz0https://orcid.org/0000-0002-7525-0384Elizabeth A Zimmermann1Bettina M Willie2https://orcid.org/0000-0003-2907-3580Svetlana V Komarova3https://orcid.org/0000-0003-3570-3147Faculty of Dentistry, McGill University, Montreal, Quebec, Canada; Shriners Hospital for Children - Canada, Montreal, Quebec, CanadaShriners Hospital for Children - Canada, Montreal, Quebec, Canada; Department of Pediatric Surgery, Montreal, Quebec, CanadaShriners Hospital for Children - Canada, Montreal, Quebec, Canada; Department of Pediatric Surgery, Montreal, Quebec, CanadaFaculty of Dentistry, McGill University, Montreal, Quebec, Canada; Shriners Hospital for Children - Canada, Montreal, Quebec, CanadaBone cells sense and actively adapt to physical perturbations to prevent critical damage. ATP release is among the earliest cellular responses to mechanical stimulation. Mechanical stimulation of a single murine osteoblast led to the release of 70 ± 24 amole ATP, which stimulated calcium responses in neighboring cells. Osteoblasts contained ATP-rich vesicles that were released upon mechanical stimulation. Surprisingly, interventions that promoted vesicular release reduced ATP release, while inhibitors of vesicular release potentiated ATP release. Searching for an alternative ATP release route, we found that mechanical stresses induced reversible cell membrane injury in vitro and in vivo. Ca2+/PLC/PKC-dependent vesicular exocytosis facilitated membrane repair, thereby minimizing cell injury and reducing ATP release. Priming cellular repair machinery prior to mechanical stimulation reduced subsequent membrane injury and ATP release, linking cellular mechanosensitivity to prior mechanical exposure. Thus, our findings position ATP release as an integrated readout of membrane injury and repair.https://elifesciences.org/articles/37812ATP releasebonemechano-adaptationmembrane injurypurinergic (P2) signallingvesicular exocytosis |
| spellingShingle | Nicholas Mikolajewicz Elizabeth A Zimmermann Bettina M Willie Svetlana V Komarova Mechanically stimulated ATP release from murine bone cells is regulated by a balance of injury and repair eLife ATP release bone mechano-adaptation membrane injury purinergic (P2) signalling vesicular exocytosis |
| title | Mechanically stimulated ATP release from murine bone cells is regulated by a balance of injury and repair |
| title_full | Mechanically stimulated ATP release from murine bone cells is regulated by a balance of injury and repair |
| title_fullStr | Mechanically stimulated ATP release from murine bone cells is regulated by a balance of injury and repair |
| title_full_unstemmed | Mechanically stimulated ATP release from murine bone cells is regulated by a balance of injury and repair |
| title_short | Mechanically stimulated ATP release from murine bone cells is regulated by a balance of injury and repair |
| title_sort | mechanically stimulated atp release from murine bone cells is regulated by a balance of injury and repair |
| topic | ATP release bone mechano-adaptation membrane injury purinergic (P2) signalling vesicular exocytosis |
| url | https://elifesciences.org/articles/37812 |
| work_keys_str_mv | AT nicholasmikolajewicz mechanicallystimulatedatpreleasefrommurinebonecellsisregulatedbyabalanceofinjuryandrepair AT elizabethazimmermann mechanicallystimulatedatpreleasefrommurinebonecellsisregulatedbyabalanceofinjuryandrepair AT bettinamwillie mechanicallystimulatedatpreleasefrommurinebonecellsisregulatedbyabalanceofinjuryandrepair AT svetlanavkomarova mechanicallystimulatedatpreleasefrommurinebonecellsisregulatedbyabalanceofinjuryandrepair |