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Tissue composition shapes differential skeletal integration strategies during axolotl limb regeneration.
Nat. Commun. 17:10826 (2026)
Limb regeneration requires rebuilding the missing structures and integrating them with stump tissues. Osteoclast-mediated tissue resorption is essential for skeletal integration during regeneration. However, it is unknown if skeletal tissue composition impacts its resorption and, if so, how it is regulated. Here, we show that osteoclast-mediated skeletal resorption is activated in amputations damaging the diaphysis, but not the epiphysis, of skeletal elements. We found that amputations in the calcified diaphysis trigger the sustained expression of RANKL and the chemokine Loc483, and that the latter is sufficient to induce osteoclast presence in non-resorbing amputations. Finally, our data suggests that the transcriptomic profile of the apical epithelial cap is impacted by the tissues injured by the amputation. Overall, our work reveals that tissue composition at the amputation plane shapes adaptations of the regenerative program, which ultimately contribute to the near-seamless tissue integration of the regenerating axolotl limb regardless of the amputation position.
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Publication type
Article: Journal article
Document type
Scientific Article
ISSN (print) / ISBN
2041-1723
e-ISSN
2041-1723
Journal
Nature Communications
Quellenangaben
Volume: 17,
Issue: 1,
Article Number: 10826
Publisher
Springer
Publishing Place
London
Reviewing status
Peer reviewed
Institute(s)
Institute of Pancreatic Islet Research (IPI)