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Understanding how tendons stay healthy and strong

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Tendon injuries can take years to properly heal. But a new study may bring us closer to one day using gene therapies to grow and repair tendons.

The research, published in the journal Proceedings of the National Academy of Sciences, looks at how tendons develop and stay healthy.

“If we understand the molecular mechanisms of tendon development, we can apply the findings to develop a new regenerative therapy for tendon diseases and injuries,” explained Hiroshi Asahara, a professor of molecular and experimental medicine at The Scripps Research Institute (TSRI) in California with joint appointments at Tokyo Medical and Dental University and the Japan Science and Technology Agency.

Asahara and his colleagues uncovered the role of a gene called Mkx in maintaining and strengthening tendons in animal models. This gene also appears to prevent a tendon condition called ossification, TSRI reported.

The research builds on previous studies showing that Mkx codes for a “transcription factor” called Mohawk (MKX), which tells cells to differentiate into tendon tissues when an embryo is first developing.

Once formed, tendons end up with just a few cells among tight bundles of collagen and elastin fibres. These fibres make tendons flexible and strong, but the lack of cells — which produce the proteins needed for regeneration — makes injuries slow to heal.

Investigating the possible role of Mkx in adult animals, Asahara and his team discovered that the gene appears to be critical for sensing mechanical stress in tendons.

The MKX transcription factor appears to respond to stretching in the tendon by forming more tenocytes, the cells needed to maintain tendon fibres, thereby keeping tendons strong.

MKX also seems to prevent tendon cells from accidentally differentiating into cartilage or bone cells, the researchers said. This is significant because the development of bone cells in the Achilles tendons and the cervical ligaments, known as ossification, causes serious clinical problems, but the molecular mechanisms behind the phenomenon were previously unclear.

“Our findings should help to understand the pathogenesis of this disease and provide therapeutic clues,” Asahara said.

The researchers believe that future gene therapies could target Mkx to strengthen tendons.

http://www.scripps.edu/news/press/2016/20160713asahara.html

http://www.pnas.org/content/113/28/7840.abstract