Insulin-like growth factor 1 (IGF1) is essential for allowing tendons to adapt to physical activity and grow properly, according to basic science research by investigators at Hospital for Special Surgery (HSS). The findings provide a strong rationale for pursuing clinical trials to explore IGF1 as a new target for treating tendon injuries in humans.
Tendons connect muscles to bone, allowing the body to move. They respond and adapt to the demands of specific activities such as walking, running or playing sports. For example, leg tendons become more spring-like in basketball players, allowing them to jump higher and with more explosive force. Tendon injuries such as Achilles tendon rupture can occur through overuse or repetitive strain and are common among athletes.
"Ruptured tendons can be catastrophic. About 30 percent of athletes with an Achilles tendon rupture are not able to return to play, and those who do return regain about 75 percent of their pre-injury ability," said senior author Christopher Mendias, PhD, ATC, an associate scientist in the Orthopaedic Soft Tissue Research Program at HSS. "There has been a lot of discussion in the NBA and other professional sports leagues about the recent increase in Achilles tendon ruptures and tendon injuries. We are also seeing an increase in tendon ruptures in the general population."
In the basic science study, published September 19, 2019, in The FASEB Journal, the HSS researchers used advanced genetics techniques to remove the IGF1 gene in cells and then monitored tendon growth. They found that without IGF1, tendons were smaller and didn't adapt like they normally would.
Next, the researchers added IGF1 to tendon cells in culture to study precisely how IGF1 affected the cells' growth processes. "Two of the ways that IGF1 affected tendon cells was through increasing cell division and stimulating the synthesis of new proteins.," said first author Nathaniel Disser, BS, a research fellow at HSS. Making new protein, such as collagen, is an important process the body uses to form tendons and other connective tissues.
In humans, growth hormone drives childhood growth and helps preserve tissues throughout adult life by maintaining adequate IGF1 levels. Human growth hormone (somatropin) is already available by prescription for treating children with growth failure due to growth hormone deficiency or adults with growth hormone deficiency. There is also another available drug called mecasermin (Increlex), which is a form of IGF1. It is used to treat children with a severe growth hormone deficiency, such as the absence of a gene to produce growth hormone.
"Overall, our study has identified that IGF1 plays an essential role in tendon growth and paves the way for future research to test whether targeting IGF1 is useful for treating painful and debilitating tendon injuries," Dr. Mendias said. "Clinical trials are required before drawing conclusions about the ability of human growth hormone to repair tendon injuries better than is possible today."
Dr. Mendias and colleagues are also currently completing a clinical trial testing the ability of human growth hormone to increase IGF1 levels to see whether that may prevent muscle atrophy in people recovering from anterior cruciate ligament (ACL) tears.
This work was supported by the National Institutes of Health under award numbers R01AR063649 & F32AR06708.
HSS is the world's leading academic medical center focused on musculoskeletal health. At its core is Hospital for Special Surgery, nationally ranked No. 1 in orthopedics (for the tenth consecutive year), No. 3 in rheumatology by U.S. News & World Report (2019-2020), and named a leader in pediatric orthopedics by U.S. News & World Report "Best Children's Hospitals" list (2019-2020). Founded in 1863, the Hospital has one of the lowest infection rates in the country and was the first in New York State to receive Magnet Recognition for Excellence in Nursing Service from the American Nurses Credentialing Center four consecutive times. The global standard total knee replacement was developed at HSS in 1969. An affiliate of Weill Cornell Medical College, HSS has a main campus in New York City and facilities in New Jersey, Connecticut and in the Long Island and Westchester County regions of New York State. In addition, HSS will be opening a new facility in Florida in early 2020. In 2018, HSS provided care to 139,000 patients and performed more than 32,000 surgical procedures, and people from all 50 U.S. states and 80 countries travelled to receive care at HSS. There were more than 37,000 pediatric visits to the HSS Lerner Children's Pavilion for treatment by a team of interdisciplinary experts. In addition to patient care, HSS leads the field in research, innovation and education. The HSS Research Institute comprises 20 laboratories and 300 staff members focused on leading the advancement of musculoskeletal health through prevention of degeneration, tissue repair and tissue regeneration. The HSS Global Innovation Institute was formed in 2016 to realize the potential of new drugs, therapeutics and devices. The HSS Education Institute is the world's leading provider of education on musculoskeletal health, with its online learning platform offering more than 600 courses to more than 21,000 medical professional members worldwide. Through HSS Global Ventures, the institution is collaborating with medical centers and other organizations to advance the quality and value of musculoskeletal care and to make world-class HSS care more widely accessible nationally and internationally. http://www.