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Philanthropic investments made by grateful patients to the Campaign to Cure Arthritis have leveraged a world first discovery. A research team at the Krembil Research Institute has discovered a pair of tissue biomarkers that directly contribute to the harmful joint degeneration associated with spine osteoarthritis. This study, published recently in the Journal of Clinical Investigation Insight, is the first to show that elevated levels of both of these biomarkers cause inflammation, cartilage destruction and collagen depletion.
“These biomarkers are actively involved in increasing inflammation and destructive activities in spine cartilage and assist in its destruction,” says principal investigator Dr. Mohit Kapoor, Senior Scientist at the Krembil Research Institute who specializes in arthritis research.
Osteoarthritis affects about three million Canadians and is characterized by a breakdown of the protective cartilage found in the body’s spine, hand, knee and hip joints. There is no known cure.
“This discovery is important because there is currently no test that can accurately detect the extent of the destruction of the joints,” says Dr. Kapoor. “Earlier detection will lead to early intervention, which can help limit irreparable damage to the patient’s cartilage.”
Stage one of research now complete
The study involved tissue biopsies from 55 patients undergoing decompression or discectomy at the Krembil Neuroscience Centre at Toronto Western Hospital. As part of the study, the research team – led by Dr. Kapoor and comprising Dr. Y. Raja Rampersaud, a clinical expert and spine surgeon and Dr. Akihiro Nakamura, a postdoctoral fellow – explored the role, function and signalling mechanisms of two tissue biomarkers: microRNA-181a-5p and microRNA-4454. RNAs regulate genes, by modifying the rate at which genes are transcribed or translated.
The researcher team screened 2,100 microRNAs and found that measuring the levels of these two specific biomarkers can help clinicians determine the stage to which the disease has progressed, and provide a tool for determining the degree of cartilage destruction.
“These are biologically active molecules,” says Dr. Kapoor. “By detecting them in the tissue biopsies, we have a tool for determining the stage of spine osteoarthritis and the degree of cartilage destruction.”
The possibilities go beyond early diagnosis
“What is really significant is we have discovered that these biomarkers are actively involved in destroying cartilage and increasing inflammation,” says Dr. Rampersaud. “Furthermore, they promote cartilage cells to die and deplete the most important component of your cartilage, which is your collagen. We’ve been able to show that by reversing or inhibiting these microRNAs, it actually changes the bad effects in the cartilage.”
The discovery represents the end of the first stage of research. The team is now investigating whether these biomarkers can be detected in the blood – which would help clinicians more simply determine the stage of spine osteoarthritis – and whether further studying the biomarkers will allow researchers to halt and reverse spine degeneration.
“The most critical aspect of this discovery is that we have found that they are active,” says Dr. Kapoor. “Now that we know what they are, we are currently looking at blocking them and restoring the joint.”
A unique environment that fosters discovery
This type of collaborative approach to research is unique to the Arthritis Program because of the unmatched concentration of basic and clinical researchers based here. The exchange of ideas among clinicians, surgeons and researchers across the four divisions of the program allows for a systemic study of the many different forms of arthritis.
“Close integration across the Arthritis Program enables us to identify how emerging insights can be applied to patient care while safely evaluating new approaches to preventing, diagnosing and treating disease,” says Dr. Rampersaud. “Collaboration is critical for us to come up with innovative ways to overcome the many challenges our patients face. Donors play a key role in fuelling these discoveries.”
Content courtesy of UHN News.