Ming-Feng Hsueh, PhD, Assistant Professor in the Department of Orthopaedics at the UNC School of Medicine, is leading innovative research entitled “Anabolic indices of matrix proteins identify regenerative small RNA intrinsic to human cartilage”—recently published in Science Advances—that reveals the human ankle’s remarkable ability to regenerate cartilage, an ability previously thought to be unique to regenerative species like salamanders and zebrafish. This discovery is especially significant given that osteoarthritis (OA), a degenerative joint disease, affects more than 7.6% of the global population and is a leading cause of disability. While current OA treatments focus on managing pain, they do little to repair the underlying joint damage.
To uncover these findings, Dr. Hsueh and his team used advanced mass spectrometry to analyze cartilage proteins and identify newly synthesized molecules. This approach enabled them to observe active tissue-building (anabolism) in ankle cartilage and to identify a key role played by small RNAs (smRNAs)—tiny molecular regulators that act like conductors of a biological orchestra, coordinating the repair process. By comparing the activity of these molecules in the ankle to those in the knee and hip, the researchers revealed why ankles are less susceptible to OA and possess superior regenerative capacity.
The research aims to translate the ankle’s natural healing mechanisms to other joints, like the knee and hip, which are more prone to degeneration. Dr. Hsueh’s long-term goal is to develop biological therapies that mimic or activate these smRNA pathways in less regenerative joints, enabling non-invasive treatments that stimulate natural repair. When asked about the future of this project and where he hopes it will, Dr. Hsueh said, “This research could revolutionize how we treat arthritis—shifting from symptom management to curative, regenerative medicine.”