Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, United States; Center for Regenerative Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, United States
Karen Carreon Paz
CRTD/ Center for Regenerative Therapies TU, Center for Molecular and Cellular Bioengineering, Technische Universität Dresden, Dresden, Germany
Congtin Nguyen
CRTD/ Center for Regenerative Therapies TU, Center for Molecular and Cellular Bioengineering, Technische Universität Dresden, Dresden, Germany
Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany; Center for Systems Biology Dresden, Dresden, Germany; Max Planck Institute for the Physics of Complex Systems, Dresden, Germany; Cluster of Excellence Physics of Life, Technische Universität Dresden, Dresden, Germany
Maritta Schuez
CRTD/ Center for Regenerative Therapies TU, Center for Molecular and Cellular Bioengineering, Technische Universität Dresden, Dresden, Germany
Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany; Center for Systems Biology Dresden, Dresden, Germany; Max Planck Institute for the Physics of Complex Systems, Dresden, Germany; Cluster of Excellence Physics of Life, Technische Universität Dresden, Dresden, Germany
Joshua D Currie
Department of Biology, Wake Forest University, Winston-Salem, United States
Department of Internal Medicine 3, Center for Healthy Aging, University Hospital Carl Gustav Carus at the Technische Universität Dresden, Dresden, Germany; Paul Langerhans Institute Dresden of Helmholtz Centre Munich, University Hospital Carl Gustav Carus at the Technische Universität Dresden, Dresden, Germany
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.