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

BACKGROUND: Although urodela amphibians completely regenerate amputated limbs, the potency of limb regeneration in mammalians is very low. In mice and humans, a digit tip regenerates, but no regeneration beyond the digit joint occurs. In this article, we describe the induction of bone formation by BMPs in the forearm, a more proximal region, of neonatal mice. Distal halves of the radius and ulna were removed from limbs amputated at the wrist level in advance, and gelatin rods containing BMPs were grafted in the space of the forearm. BMP-7 and BMP-2 were effective.

RESULTS: The induction of bone formation depended on the amount of BMP-7 in grafted gelatin gels. BMP-7 at over 320 ng/limb induced long bones within 10 days. Cartilage formation was always observed before the bone formation as in the case of normal limb development. The origin of cells responsive to BMP-7 is not clear, but the formation of large bone tissues in a relatively short time suggests a wide distribution of precursor cells in the limbs. Grafting of dye-stained mesenchymal tissue fragments suggested that mesenchymal tissues other than the dermis, bone, and joint cartilage are responsive to BMP-7 and form cartilage/bone. Two long bones induced were arranged in parallel fashion in many cases like the radius and ulna. An agonist of hedgehog promoted the formation of bones in the presence of BMP-7. Furthermore, bone elements were fused to stump bones to form a single bone.

CONCLUSIONS: The results suggest the potency of bone pattern regeneration in the amputated forearm of a neonatal mouse.