Camilo Riquelme-Guzmán1, Maritta Schuez1, Alexander Böhm1, Dunja Knapp1, Sandra Edwards-Jorquera1, Alberto S Ceccarelli2, Osvaldo Chara2,3,4, Martina Rauner5,6, Tatiana Sandoval-Guzmán1,6. 1. CRTD/Center for Regenerative Therapies TU Dresden, Technische Universität Dresden, Dresden, Germany. 2. System Biology Group (SysBio), Institute of Physics of Liquids and Biological Systems (IFLySiB), National Scientific and Technical Research Council (CONICET) and University of La Plata, La Plata, Argentina. 3. Instituto de Tecnología, Universidad Argentina de la Empresa (UADE), Buenos Aires, Argentina. 4. Center for Information Services and High Performance Computing (ZIH), Technische Universität Dresden, Dresden, Germany. 5. Department of Medicine III, Universitätsklinikum Dresden, Dresden, Germany. 6. Center for Healthy Aging, Universitätsklinikum Dresden, Dresden, Germany.
Abstract
BACKGROUND: The axolotl is a key model to study appendicular regeneration. The limb complexity resembles that of humans in structure and tissue components; however, axolotl limbs develop postembryonically. In this work, we evaluated the postembryonic development of the appendicular skeleton and its changes with aging. RESULTS: The juvenile limb skeleton is formed mostly by Sox9/Col1a2 cartilage cells. Ossification of the appendicular skeleton starts when animals reach a length of 10 cm, and cartilage cells are replaced by a primary ossification center, consisting of cortical bone and an adipocyte-filled marrow cavity. Vascularization is associated with the ossification center and the marrow cavity formation. We identified the contribution of Col1a2-descendants to bone and adipocytes. Moreover, ossification progresses with age toward the epiphyses of long bones. Axolotls are neotenic salamanders, and still ossification remains responsive to l-thyroxine, increasing the rate of bone formation. CONCLUSIONS: In axolotls, bone maturation is a continuous process that extends throughout their life. Ossification of the appendicular bones is slow and continues until the complete element is ossified. The cellular components of the appendicular skeleton change accordingly during ossification, creating a heterogenous landscape in each element. The continuous maturation of the bone is accompanied by a continuous body growth.
BACKGROUND: The axolotl is a key model to study appendicular regeneration. The limb complexity resembles that of humans in structure and tissue components; however, axolotl limbs develop postembryonically. In this work, we evaluated the postembryonic development of the appendicular skeleton and its changes with aging. RESULTS: The juvenile limb skeleton is formed mostly by Sox9/Col1a2 cartilage cells. Ossification of the appendicular skeleton starts when animals reach a length of 10 cm, and cartilage cells are replaced by a primary ossification center, consisting of cortical bone and an adipocyte-filled marrow cavity. Vascularization is associated with the ossification center and the marrow cavity formation. We identified the contribution of Col1a2-descendants to bone and adipocytes. Moreover, ossification progresses with age toward the epiphyses of long bones. Axolotls are neotenic salamanders, and still ossification remains responsive to l-thyroxine, increasing the rate of bone formation. CONCLUSIONS: In axolotls, bone maturation is a continuous process that extends throughout their life. Ossification of the appendicular bones is slow and continues until the complete element is ossified. The cellular components of the appendicular skeleton change accordingly during ossification, creating a heterogenous landscape in each element. The continuous maturation of the bone is accompanied by a continuous body growth.
Authors: A Polikarpova; A Ellinghaus; O Schmidt-Bleek; L Grosser; C H Bucher; G N Duda; E M Tanaka; K Schmidt-Bleek Journal: NPJ Regen Med Date: 2022-06-30