Abstract
In spite of numerous investigations of regenerating salamander limbs, little attention has been paid to the details of how joints are reformed. An understanding of the process and mechanisms of joint regeneration in this model system for tetrapod limb regeneration would provide insights into developing novel therapies for inducing joint regeneration in humans. To this end, we have used the axolotl (Mexican Salamander) model of limb regeneration to describe the morphology and the expression patterns of marker genes during joint regeneration in response to limb amputation. These data are consistent with the hypothesis that the mechanisms of joint formation whether it be development or regeneration are conserved. We also have determined that defects in the epiphyseal region of both forelimbs and hind limbs in the axolotl are regenerated only when the defect is small. As is the case with defects in the diaphysis, there is a critical size above which the endogenous regenerative response is not sufficient to regenerate the joint. This non-regenerative response in an animal that has the ability to regenerate perfectly provides the opportunity to screen for the signaling pathways to induce regeneration of articular cartilage and joints.
Highlights
Many different approaches utilizing a variety of model systems have attempted to regenerate joint structures
Animals and Surgical Procedures Experiments were performed on axolotls (Ambystoma mexicanum) measuring 8–14 cm from snout to tail tip that were spawned at the University of California, Irvine or the Ambystoma Genetic Stock Center at the University of Kentucky
Joints of the Axolotl As reported previously [4,9], the basic anatomy of axolotl joints with apposed articular surfaces between adjacent long bones that are encapsulated by connective tissues was very similar to mammals (Fig. 1)
Summary
Many different approaches utilizing a variety of model systems have attempted to regenerate joint structures. Most of these efforts have focused on engineering specific joint tissues, articular cartilage in particular, that can be used for grafting to repair damaged joints. These efforts have been limited by the reality that cartilage has a limited endogenous regenerative response and forms fibrocartilage (scar tissue) in the joint in response to injury (see [1]). Surgical defects to the articular cartilage of the axolotl (Mexican Salamander) knee joint made by resection of the medial femoral condyle to the level of the metaphysis regenerate intrinsically [4]. The intrinsic regenerative response of the axolotl provides an opportunity to discover the mechanisms for inducing repair and regeneration of articular cartilage and joints
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