Collaborative Study Reaches New Heights

Posted on: Wednesday, 06/06/2018

NASA Research

BACKGROUND

An estimated 54 million adults in the U.S. are currently at risk for osteoporosis and fractures. This number balloons to more than 200 million affected worldwide. 

Osteoporosis is a bone disease that occurs when individuals start to lose bone mass and/or stop making bone, which leads to increased risk of fracture and mobility. For people with osteoporosis, quality of life can decline considerably and the financial burden can be devastating. Current FDA-approved therapies do little to prevent and treat the condition. Most therapies stop the process, yet none are able to grow bone. Furthermore, not a single therapy exists that addresses dental osteoporosis, which can lead to tooth loss, failure of implants, and loosening of dentures.

In 1996, Dr. Kang Ting, professor and chair of orthodontics at the UCLA School of Dentistry, made a landmark discovery of the protein NELL-1, which pushed osteoporosis therapy research forward decades. He found that the protein has a dual effect. It reduces the 

function of the cells that break down bone, and it jump starts the creation of bone growth in stem cells. 

Re-enacting the onset of osteoporosis in a university lab is time-consuming and expensive. Dr. Ting and his NELL-1 collaborator, Dr. Chia Soo, professor of plastic and reconstructive surgery and orthopaedic surgery at the UCLA Health System, received a windfall in 2015 when they were awarded funding from the Center for Advancement of Science in Space (CASIS). The grant would help take their groundbreaking work to new heights. The pair would be able to send their osteoporotic mouse-models into space to test the NELL-1 therapy for the prevention of bone loss.

METHOD 

In space, bone loss significantly increases due to the lack of gravity. Without gravity’s pressure, astronauts can lose around 1.5 percent of their bone mass each month in space. This is 36 times as much as bone loss on Earth, which is 0.5 percent of bone loss per year after the age of 50. Therefore, space is an ideal testing environment for NELL-1’s effect on bone density and it could greatly increase the therapy’s development for human applications.

To prepare for the study, the duo called on Dr. Ben Wu, professor and chair of advanced prosthodontics at the UCLA School of Dentistry, who modified the NELL-1

molecule to make osteoporosis treatment possible in space. Dr. Wu is internationally recognized for engineering cells, proteins, and genes to promote repair and regeneration of hard and soft tissues. Dr. Wu’s team was able to chemically modify NELL-1 to stay active longer in the body. Also, they engineered the NELL-1 protein with a special molecule that binds to bone, so the molecule directs NELL-1 to its correct target. Dr. Jin Hee Kwak, associate adjunct professor of orthodontics at the UCLA School of Dentistry, was added to the team to act as a co-managing PI and also provide expertise on administering NELL-1 to target dental bones.

The team, along with dozens of residents at the dental school, worked around the clock to prepare for a summer 2017 launch. On June 3, 2017, 40 rodents were successfully launched into space, where they would live for the next four weeks at the International Space Station (ISS). Notably, this event marked the first time that American researchers brought back rodents from ISS that were all alive and healthy.

After living in microgravity and receiving NELL-1 injections, half of the rodents returned from space and landed in the Pacific Ocean off the coast of Baja California. That set of mice was transported back to UCLA where they continued to receive the NELL-1 drug for an additional four weeks. The remaining half of the rodents that stayed in the space station received an additional four-week dosage of the drug before being returned to UCLA later that summer.

IMPACT

Osteoporosis is a significant public health problem and can lead to a number of health issues and conditions, including immobilization, stroke, cerebral palsy, muscular dystrophy, spinal cord injury, and jaw resorption after tooth loss. Although the team is still compiling and analyzing data, there is promising evidence that NELL-1 can effectively combat microgravity bone loss. Later this year, the researchers plan to present their findings at two space research conferences. This study has significant translational potential for new insights into the prevention of osteoporosis as well as for the regeneration of massive bone damage that can occur in wounded military personnel.

FUNDING

This research is supported by extramural grants from the Center for the Advancement of Science in Space, the National Institute of Dental and Craniofacial Research, the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the California Institute for Regenerative Medicine, and the American Association of Orthodontists Foundation. Additional intramural support is provided by the UCLA/Orthopaedic Hospital Department of Orthopaedic Surgery, the UCLA Division of Plastic and Reconstructive Surgery, the UCLA School of Dentistry, and the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA.