UC Davis researchers discover cartilage-stabilizing protein also drives cartilage growth
New finding is critical to expanding osteoarthritis treatments
UC Davis researchers have discovered that the protein responsible for the structural integrity of cartilage has a major role in creating it as well. The protein -- known as COMP for cartilage oligomeric matrix protein -- binds to growth-promoting molecules and links them with the cellular framework that forms cartilage.
"Researchers primarily view COMP as a bridge that holds the extracellular pieces of cartilage together," said Dominik Haudenschild, assistant professor of orthopaedic surgery at UC Davis and senior author of the study. "Now we know that it also actively captures and delivers to that cellular framework the specialized growth factors that determine how and when cartilage is created."
The investigators also discovered that COMP increases the production of growth factors called transforming growth factor-beta, or TGF-β, creating a supportive environment for the development of new cartilage.
Haudenschild's research focuses on identifying biological pathways that could lead to earlier diagnosis and new interventions for osteoarthritis, which occurs when the cartilage cushion in joints degrades. The disease is typically diagnosed when that cushion is almost gone and bone is rubbing against bone. At that point, surgical repairs and pain management are the best treatment options.
"The more we know about what it takes to create and maintain healthy cartilage, the more opportunities there are to develop drugs that preserve and encourage that process," he said.
The current study, published in the December 16 issue of the Journal of Biological Chemistry, has important implications for tissue engineering as well.
"There is a big drive now for lab-developed substitutes that could replace natural cartilage," said Haudenschild. "It's possible that COMP could be used to enhance the tissue-building process. Stimulating COMP production in cells could also help concentrate the growth factors that promote this process."
In conducting the study, Haudenschild and his team used electron microscopy to determine the five-armed structure of COMP. They then studied the binding of COMP and TGF-β in cell cultures, revealing that COMP can bind up to two TGF-β molecules per arm. They also looked at the effects of COMP on the production of additional TGF-β, noting that COMP has a key role in regulating TGF-β activity within the cellular framework for cartilage.
In additional experiments, the team noted the optimal conditions for COMP binding, suggesting that research aimed at finding new treatments for osteoarthritis focus on recreating these conditions. The outcomes indicate that pH and manganese both improve COMP's natural ability to bind TGF-β.
Haudenschild and his colleagues are currently developing animal-model studies of osteoarthritis. Their hope is to further establish the role of COMP in healthy cartilage and look for ways to advance its activity in joints where osteoarthritis has already set in.
"We hope these basic research findings will lead to interventions that prevent the breakdown of cartilage that causes osteoarthristis," said Haudenschild.
In addition to Haudenschild, UC Davis study authors were Eunmee Hong, Jasper Yik, Kaylene Snow, Chitrangada Acharya, Yoshikazu Takada and Paul Di Cesare. Other authors were Brett Chromy of Lawrence Livermore National Laboratory and Matthias Mörgelin of Sweden's Lund University.
The research was supported by UC Davis departmental startup funds and by the Swedish Research Council. Recombinant human BMP-7 was donated by Stryker Biotech.
The UC Davis Department of Orthopaedic Surgery provides comprehensive medical and surgical care of the musculoskeletal system for both adults and children. As a leading West Coast center for orthopaedic care, the department provides a full spectrum of treatment specialties, including joint reconstruction, microvascular surgery, sports medicine and pediatric orthopaedics. UC Davis was ranked 35th among orthopaedic surgery departments nationwide by U.S. News & World Report for 2010-11. For more information, visit the department's website.