Analogous cellular contribution and healing mechanisms following digit amputation and phalangeal fracture in mice.

Lindsay A Dawson,Michelle Sauque,Teresa Palkowski,Ken Muneoka,Maegan Pela,Jennifer Simkin

doi:10.1002/reg2.51

Abstract

Regeneration of amputated structures is severely limited in humans and mice, with complete regeneration restricted to the distal portion of the terminal phalanx (P3). Here, we investigate the dynamic tissue repair response of the second phalangeal element (P2) post amputation in the adult mouse, and show that the repair response of the amputated bone is similar to the proximal P2 bone fragment in fracture healing. The regeneration‐incompetent P2 amputation response is characterized by periosteal endochondral ossification resulting in the deposition of new trabecular bone, corresponding to a significant increase in bone volume; however, this response is not associated with bone lengthening. We show that cells of the periosteum respond to amputation and fracture by contributing both chondrocytes and osteoblasts to the endochondral ossification response. Based on our studies, we suggest that the amputation response represents an attempt at regeneration that ultimately fails due to the lack of a distal organizing influence that is present in fracture healing.

Highlights

Mammals, including humans and mice, lack the extensive regenerative capacity of urodele amphibians but are capable of regenerating the distal region of the terminal phalanx (P3) following amputation (Douglas 1972; Illingworth 1974; Borgens 1982)
The mouse digit regeneration model is unique in part because it occurs in a mammal, and because it provides a way to explore amputation injury responses that are either regeneration-competent or regeneration-incompetent
We have shown that bone morphogenetic protein 2 (BMP-2) induces a regenerative response in the amputated P2 bone that involves the formation of a transient blastema, the creation of an endochondral ossification center, and the patterned extension of the stump bone (Yu et al 2012)

Summary

Introduction

Mammals, including humans and mice, lack the extensive regenerative capacity of urodele amphibians but are capable of regenerating the distal region of the terminal phalanx (P3) following amputation (Douglas 1972; Illingworth 1974; Borgens 1982). In mice, this response occurs in fetal, neonatal, and adult digits, and involves the formation of a blastema of undifferentiated and proliferating cells (Reginelli et al 1995; Han et al 2008; Fernando et al 2011). Schotteand Smith (1959) found that the bone healing response differed between mid-diaphyseal amputations versus amputation levels

Methods

Results

Conclusion