Discovery Knows No Bounds

Discovery knows no bounds

© Copyright 2019 Regenerative Medicine Minnesota

Repair & regeneration of human cartilage damaged by osteoarthritis

Research Grant Recipient: Elizabeth W. Bradley, PhD

Grant Period: 2015-2017

Award Value: $500,000

Site: Mayo Clinic

Click here to read Bradley's First Year Progress ReportClick here to see progress video Click here to read Bradley's Final Progress Report

Osteoarthritis is one of the leading causes of disability in the US today. The disease occurs when articular cartilage in a joint degenerates. Articular cartilage is the smooth, white tissue that covers the ends of bones where they come together to form joints. It doesn’t regenerate in the same way as other tissue in the body. Articular cartilage allows the bones to glide over each other with very little friction, and it’s essential to movement. As osteoarthritis takes hold, it becomes progressively more painful and difficult to move.

The only way to currently cure osteoarthritis is through joint replacement surgery. It’s not ideal, we don’t have implants available for every joint, and infection is always a risk. Even when a joint replacement is available, it doesn’t last a lifetime. That means young and middle age adults will need to undergo another surgery again later in life.

A treatment that could cure the disease by promoting articular cartilage to heal in the same way as other tissues in the body would give countless patients a less intrusive medical alternative to a joint replacement surgery. Researchers have found a gene, the Phlpp1 (pronounced “flip”) that stops regeneration in cartilage. If we can block the Phlpp action, then cartilage could possibly repair itself. That means there could be a treatment for osteoarthritis other than joint replacement.

Two chemical inhibtors have been found to block Phlpp activity and slow down the progression of osteoarthritis in mice. That’s a great step, but researchers don’t know if that would work in people. The focus of this grant is to test whether or not human articular cartilage can be regenerated when the Phlpp actions are blocked. It’s called the “Phlpp knockout”, and it could be an incredible option for osteoarthritis patients.

This grant will support researchers testing drugs to treat osteoarthritis and support the Phlpp knockout in humans. There are three possibilities that the team will observe. The first is a drug made of tiny molecules that block the gene stopping cartilage from regenerating. The second idea is to find out if it’s possible for adult stem cells to grow into cartilage by blocking the Phlpp activity. Third, this research will look at how controlling Phlpp activity could work on neocartilage, engineered tissue that could replace degenerated articular cartilage.

The researchers working on this grant are the first in the world to identify the Phlpp activity in cartilage regeneration. This is one of the only promising treatments for osteoarthritis being worked on today, and it puts Minnesota at the forefront of cartilage regeneration.

The only way for new osteoarthritis treatments to be developed is through further research funded by this grant. As federal support dries up, grants like this become increasingly more important. Therefore, the advancement of this research, with Regenerative Medicine Minnesota funding, could benefit osteoarthritis patients for generations to come.

Dr. Elizabeth W. Bradley is an assistant professor in the Department of Orthopedic Surgery at the Mayo Clinic in Rochester, Minnesota. She has developed a broad background in biochemistry and cell biology and has worked extensively with the Phlpp1 knockout in mice to prepare for this study on human articular cartilage. Bradley earned her PhD in Biochemistry at the Mayo Clinic in 2008 and served in fellowship and research positions at the University of Connecticut, Mayo Clinic, and the University of Minnesota before becoming a faculty professor at Mayo. She also earned many distinctions, particularly the K01 award for evaluating the effects of Phlpp1 on cartilage development from the National Institute of Health (NIH).

Dr. Jennifer J. Westendorf is the Margaret Amini Professor for Orthopedic Regenerative Medicine Research at Mayo Clinic in Rochester, Minnesota. She has extensive experience and expertise on skeletal development, and her independent and NIH-funded research lab has focused on identifying and analyzing the impact that Phlpp1 has on cartilage development and osteoarthritis disease progression. Their preliminary data show that Phlpp1 inhibition may prevent articular cartilage degradation in mouse models, findings that have led them to launch this RMM-funded study on human articular cartilage. Westendorf earned her PhD in Immunology at the Mayo Clinic in 1996 and previously served as a professor at the University of Minnesota. She also serves as an ad-hoc grant reviewer and editorial board member of multiple journals.