19 May 2022

Supersonic regeneration trigger

In the study, Maxwell Serovoki and his colleagues from the Keck School of Medicine at the University of Southern California studied the ability of mice to repair large bone defects. They observed an increase in the activity of the gene named after the hero of the eponymous series of old computer games "supersonic hedgehog" (Sonic hedgehog, Shh), which plays an important role in the formation of the skeleton in embryos, but was not previously associated with the restoration of damage in adults. In their experiments, it turned out that Shh triggers the healing of large areas of bones, but not in the closure of small fractures.

This means that large-scale bone regeneration requires the participation of an embryonic development program involving Shh, while small injuries heal with the help of another recovery program that is not involved in embryogenesis.

Shh.jpg

Segmental resection of the rib bone with a thickness of 3 mm was performed, adjacent periosteal and muscle tissues were left intact. 0 dpi (days post injury, days after injury) – rib on the day of resection; 7 dpi – cartilage tissue (blue color) overlaps the defect; 14 dpi – bone callus turned into bone (red color), and some amount of cartilage remained near the incision sites; 28 dpi – rib recovered to its original appearance.

In mice, Shh activity increased briefly after resection of the central part of the rib, and then quickly returned to normal levels within 5 days. Despite its transient nature, this Shh activity is a prerequisite for the successful construction of a callus, which is then transformed into bone and restores the missing part of the rib.

In mice with the Shh gene knocked out, a callus did not form. In contrast, mice in which Shh was active at the time of injury but silenced after 5 days showed normal rib recovery. The related gene Smoothened (Smo) was also required only during the first 5 days of the healing process.

The researchers expected that the source Shh will be specific progenitor cells, which, as the group previously showed, are necessary for the healing of large injuries and which are located in the periosteum. But instead, they found that the source Shh is a population of mesenchymal stem cells. An increase in Shh activity in them, apparently, serves as a signal for the accumulation of periosteal stem cells involved in the healing process in the area of damage.

This discovery can form the basis for the therapy of large injuries that occur in road accidents, military operations or after resection of a bone associated with a tumor.

Article by M.A.Serowoky et al. A murine model of large-scale bone regeneration reveals a selective requirement for Sonic Hedgehog published in the journal NPJ Regenerative Medicine. Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru Based on the materials of the Keck School of Medicine of USC: For large bone injuries, it's Sonic hedgehog to the rescue.


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