laboratory mouse
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Two proteins appear to be linked to regeneration

A pair of proteins could help regenerate amputated limbs. When applied to amputated toes, the proteins encouraged both bone and joint growth in mice.

Joints are structurally complex, so even for animals that can regrow their lost limbs, rarely can they regenerate their joints as well.

Ken Muneoka at Texas A&M University and his colleagues had previously regenerated bones in mice after they were amputated by treating the stump with a bone-growing protein, BMP2. But joint structures never formed.

The team suspected that another bone-growing protein, BMP9, could be essential in joint building. So they tried applying the protein to mice that had their toes amputated. After three days, over 60 per cent of the stump bones formed a layer of cartilage, as seen in joints, at the end of the bones.
mouse toe regeneration
© Ling Yu, Lindsay A. Dawson, et. al.Partial description of bone morphogenetic protein 9 (BMP9) stimulates regeneration of joint structures. a Bmp9 transcripts are localized to digit joints undergoing cavitation (arrowhead) in E18.5 embryos. b P2 level amputation of neonatal digits is used to test for induced regeneration. Following amputation (red line) at postnatal day 3 (PN3), epidermal closure is completed 4 days later (PN7), and an agarose microcarrier bead (blue dot) is implanted between the wound epidermis and the stump. c Microcomputed tomography (µCT) rendering of a BMP9-treated digit showing regeneration of a skeletal element articulating with the stump after 4 weeks (PN35).
The result was more effective when the team treated the wounds first with BMP2 and then BMP9 a week later. Not only did the bones regrew, they also formed more complete joint structures with part of the new bones attached to them. Although the method does not yet produce a full toe.

"Our study is transformational," says Muneoka. He suggests this experiment proves that even though mammals can't regenerate body parts, we have cells that know how to and what to grow. "They can do it, they just don't do it. So, we have to figure out what's constraining them," he says.

Because human skeletal structure is very similar to that of mouse, Muneoka says he is optimistic that one day we will be able to help amputees regrow their limbs. But more studies need to be done before any trials in humans, he says.

Journal reference: Nature Communications, DOI: 10.1038/s41467-018-08278-4