Scleraxis found vital for knitting muscles and bones together

September 8, 2017
Compared to ScxCre/+ mouse, ScxCre/Cre mouse is small. The forelimb autopod of ScxCre/Cre KI neonates was locked in a dorsal flexure (arrow). Credit: Hiroshima University

In vertebrates, bodily support and movement requires bones and muscles. Muscles pull and push, contract and relax - and bones respond accordingly. Taken together they form the musculoskeletal system.

But, while much is known about each of these system's disparate parts, less is known about the joining mechanisms tying them together into an intricate whole.

Hiroshima University researchers, keen to resolve these linking regions and develop regeneration therapies based on stem , have made a major breakthrough in understanding.

Professor Chisa Shukunami, and Specially Appointed Research Associate Yuki Yoshimoto, of HU's Graduate School of Biomedical and Health Sciences, have found that the Scleraxis (Scx) "transcription factor" – a type of protein controlling production of genetic information in cells – is vital for the of muscle-bone joining regions.

Scx has already been found to exist throughout embryonic development in tendons – the cords of strong white fibrous tissue that connect muscle to bones, and ligaments - bundles of tough, fibrous, elastic collagen that act as binding and support straps for joints. It is also known to be expressed for a limited time in the specialized cartilage that connects ligaments and tendons to bones.

However, the latest study from HU is the first time that Scx's necessity for maturation of these components has been observed.

The HU researchers determined Scx's necessity by creating genetically modified mice and observing their development in the embryo. These "ScxCre knock-in" mice, had their Scx expression capabilities modified so they instead produced the enzyme "Cre."

Overall, the mice devoid of Scx developed to be smaller and lacked mass and definition as a result of undeveloped regions. Credit: Hiroshima University

In the embryo Cre was thus produced in the same tissues as Scx would normally be, but without any of Scx's joint making potential. The developing mice devoid of Scx were then observed alongside developing embryos possessing natural Scx expressing capabilities.

Those lacking Scx were seen to be undeveloped in the entheseal cartilage regions – where ligaments and tendons join to bones. This was particularly noticeable in the rib cage, knees, heels, and between the vertebrae, and also in the limbs where the tuberosity – the protruding bits of to which muscles are attached - was absent.

In addition, the cell surface markers, proteins that indicate cell type, for mature ligaments and tendons were missing, and the tendons and ligaments in the knee, back, tail, and heel were all small and deficient.

Overall, the mice devoid of Scx developed to be smaller and lacked mass and definition as a result of these undeveloped regions.

These results highlight the functional importance of both the persistent expression of Scx for the formation of tendons and ligaments, and also that of the short burst of Scx expression that precedes the formation of entheseal cartilage that connects and ligaments to bones.

The researchers at HU are keen to employ Scx's role in cell differentiation to develop stem cell therapies for regenerating parts of the body that are notoriously difficult to repair.

Potential applications could include regeneration of worn joints in the elderly, and transplants enabling sports stars to make a speedy return to the field after injuries that could once have ended a career.

Explore further: Gelatin supplements, good for your joints?

More information: Yuki Yoshimoto et al. Scleraxis is required for maturation of tissue domains for proper integration of the musculoskeletal system, Scientific Reports (2017). DOI: 10.1038/srep45010

Related Stories

Gelatin supplements, good for your joints?

December 20, 2016
A new study from Keith Baar's Functional Molecular Biology Laboratory at the UC Davis College of Biological Sciences and the Australian Institute of Sport suggests that consuming a gelatin supplement, plus a burst of intensive ...

Making lab-grown tissues stronger

October 30, 2014
Lab-grown tissues could one day provide new treatments for injuries and damage to the joints, including articular cartilage, tendons and ligaments.

Tendon, heal thyself: Study reveals gene crucial in keeping tendons healthy

July 13, 2016
With the Rio Olympics just weeks away, many are wondering how Jamaican sprinter Usain Bolt will perform. Bolt is the fastest runner ever timed, but he's also been nursing a tendon injury—the kind of injury that can take ...

Recommended for you

Hibernating ground squirrels provide clues to new stroke treatments

November 17, 2017
In the fight against brain damage caused by stroke, researchers have turned to an unlikely source of inspiration: hibernating ground squirrels.

Molecular guardian defends cells, organs against excess cholesterol

November 16, 2017
A team of researchers at the Harvard T. H. Chan School of Public Health has illuminated a critical player in cholesterol metabolism that acts as a molecular guardian in cells to help maintain cholesterol levels within a safe, ...

Prototype ear plug sensor could improve monitoring of vital signs

November 16, 2017
Scientists have developed a sensor that fits in the ear, with the aim of monitoring the heart, brain and lungs functions for health and fitness.

Ancient enzyme could boost power of liquid biopsies to detect and profile cancers

November 16, 2017
Scientists are developing a set of medical tests called liquid biopsies that can rapidly detect the presence of cancers, infectious diseases and other conditions from only a small blood sample. Researchers at The University ...

FDA to crack down on risky stem cell offerings

November 16, 2017
U.S. health authorities announced plans Thursday to crack down on doctors pushing stem cell procedures that pose the gravest risks to patients amid an effort to police a burgeoning medical field that previously has received ...

Engineering the gut microbiome with 'good' bacteria may help treat Crohn's disease

November 15, 2017
Penn Medicine researchers have singled out a bacterial enzyme behind an imbalance in the gut microbiome linked to Crohn's disease. The new study, published online this week in Science Translational Medicine, suggests that ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.