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Related Experiment Video

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Adult Mouse Digit Amputation and Regeneration: A Simple Model to Investigate Mammalian Blastema Formation and Intramembranous Ossification

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Published on: July 12, 2019

Bone pattern formation in mouse limbs after amputation at the forearm level.

¹Department of Developmental Biology and Neurosciences, Graduate School of Life Sciences, Tohoku University, Sendai, Japan. ide@m.tohoku.ac.jp

Developmental Dynamics : an Official Publication of the American Association of Anatomists

|January 26, 2012

Summary

Bone morphogenetic proteins (BMPs) can induce bone formation in neonatal mouse forearms, promoting regeneration beyond digit tips. This finding suggests potential for enhanced limb regeneration in mammals.

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Area of Science:

Regenerative Medicine
Developmental Biology
Mammalian Limb Regeneration

Background:

Mammalian limb regeneration is limited, unlike in amphibians.
Limb regeneration in mice and humans typically only regenerates digit tips.
Bone morphogenetic proteins (BMPs) show potential for inducing bone formation in mammalian limbs.

Purpose of the Study:

To investigate the potential of BMPs to induce bone formation in the mammalian forearm.
To determine the effectiveness of different BMPs (BMP-7 and BMP-2) in promoting bone regeneration.
To explore the cellular mechanisms and factors influencing BMP-induced bone formation.

Main Methods:

Amputation of distal forearms in neonatal mice.
Grafting of gelatin rods containing BMP-7 or BMP-2 into the amputation site.
Administration of hedgehog pathway agonist in conjunction with BMP-7.
Tracking of cell origins using dye-stained mesenchymal tissue fragments.

Main Results:

BMP-7, at concentrations over 320 ng/limb, induced long bone formation within 10 days.
Cartilage formation preceded bone formation, mimicking normal limb development.
Mesenchymal tissues, excluding dermis, bone, and joint cartilage, responded to BMP-7.
Hedgehog pathway activation enhanced BMP-7-induced bone formation.
Induced bones were arranged in parallel and fused with stump bones.

Conclusions:

BMPs can induce significant bone pattern regeneration in amputated neonatal mouse forearms.
This study demonstrates the potential for promoting more extensive limb regeneration in mammals.
The findings suggest a broader distribution of BMP-responsive precursor cells in mammalian limbs.