Osteoclast-mediated resorption primes the skeleton for successful integration during axolotl limb regeneration
- Technische Universität Dresden, Germany
- Harvard University, United States
- European Molecular Biology Laboratory, Spain
- Max Planck Institute of Molecular Cell Biology and Genetics, Germany
- Wake Forest University, United States
Abstract
Early events during axolotl limb regeneration include an immune response and the formation of a wound epithelium. These events are linked to a clearance of damaged tissue prior to blastema formation and regeneration of the missing structures. Here, we report the resorption of calcified skeletal tissue as an active, cell-driven and highly regulated event. This process, carried out by osteoclasts, is essential for a successful integration of the newly formed skeleton. Indeed, the extent of resorption is directly correlated with the integration efficiency and treatment with zoledronic acid resulted in osteoclast function inhibition and failed tissue integration. Moreover, we identified the wound epithelium as a regulator of skeletal resorption, likely releasing signals involved in recruitment/differentiation of osteoclasts. Finally, we reported a correlation between resorption and blastema formation, particularly, a coordination of resorption with cartilage condensation. In sum, our results identify resorption as a major event upon amputation, playing a critical role in the overall process of skeletal regeneration.
Data availability
No dataset have been generated for this manuscript.
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Wound epidermis-dependent transcriptional programsNCBI GeneExpression Omnibus, GSE132317.
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Blastemal progenitors modulate immune signaling during early limb regenerationNCBI GeneExpression Omnibus, GSE111213.
Article and author information
Author details
Camilo Riquelme-Guzmán
Tatiana Sandoval-Guzman
Funding
Deutsche Forschungsgemeinschaft (SA 3349/3-1)
- Camilo Riquelme-Guzmán
- Tatiana Sandoval-Guzman
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All procedures were performed according to the Animal Ethics Committee of the State of Saxony, Germany, and the Institutional Animal Care and Use Committee (IACUC) Guidelines at Harvard University (Protocol 11-32).
Copyright
© 2022, Riquelme-Guzmán et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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