Tendon injuries, as many athletes will know, are often difficult to treat, and researchers are keen to discover why. Now, new animal research suggests a gene that plays an important role in tendon development in early life may also play a key role in keeping the tissue healthy in the adult stage. The team behind the discovery suggests it could lead to gene therapies for tendon diseases and injuries.
The team, comprising researchers from Japan’s Tokyo Medical and Dental University and the Japan Science and Technology Agency, also in Tokyo, reports the finding in the Proceedings of the National Academy of Sciences (PNAS).
Senior and corresponding author Hiroshi Asahara, a professor of molecular and experimental medicine at The Scripps Research Institute in La Jolla, CA, also holds posts in both Tokyo research centers. He says:
“Our findings should help to understand the pathogenesis of this disease and provide therapeutic clues.”
Tendons are tight bundles of collagen and elastin fibers whose resilience and elasticity helps to make tendons strong and flexible.
However, there are not many cells among the fibers once the tendon is fully formed in adults.
Lack of cells means there are few “protein factories” to produce the proteins needed to heal any injured or damaged tissue.
Mkx keeps tendons strong and healthy in adulthood
The new study extends findings from previous research that shows a gene called Mkx, which codes for the “transcription factor” Mohawk (MKX), is active during embryo formation, where it instructs cells to differentiate into tendon tissues.
Using rat models, Prof. Asahara and colleagues discovered that Mkx is also active in the adult stages of life, where it helps to keep tendons strong and healthy.
The researchers found that lack of Mkx accelerates the formation of cartilage or bone cells, which leads to “ossification,” a debilitating condition where tendon tissue develops bony masses.
Another interesting observation was that Mkx appears to be important for sensing mechanical stress in tendons through adulthood and for the response that keeps them strong.
It appears that when the tendon is stretched, the MKX transcription factor responds by generating more tenocytes, the cells that maintain the tendon fibers.
The researchers believe their findings will lead to gene therapies that target Mkx as a way to strengthen tendons.
In their study, the team used a new gene-editing tool called CRISPR/Cas9 to manipulate Mkx in the rats. This in itself is a significant achievement, as rat embryonic stem cells are notoriously difficult to manipulate for this kind of research.
“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.”
Prof. Hiroshi Asahara