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Researchers discover molecular markers of spine osteoarthritis that contribute to joint damage.
Posted On: August 15, 2016
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Cartilage—the smooth, protective tissue that protects the ends of bones where they meet at a joint—breaks down and wears away in people with osteoarthritis, causing pain, swelling and loss of motion.
Osteoarthritis (OA) affects about three million Canadians and leads to the breakdown of the protective cartilage found in the spine, hand, knee and hip joints. The identification of biological markers (“biomarkers”) could be used to develop new preventative therapies; however, there have been no known biomarkers of spine OA, until now.
A team led by Krembil Senior Scientist Dr. Mohit Kapoor, including postdoctoral fellow Dr. Akihiro Nakamura and Krembil Clinician Investigator Dr. Y. Raja Rampersaud, recently analyzed tissue biopsies from 55 patients with spine OA. They screened 2,100 biological molecules known as microRNAs and found that two of these—microRNA-181a-5p and microRNA-4454—may be able to help clinicians determine the severity of spine OA. The study also revealed that elevated levels of these biomarkers may actually be involved in the underlying mechanisms leading to inflammation, cartilage destruction and collagen depletion.
"The most critical aspect of this discovery is that we have found that these two molecules are actively involved in increasing inflammation and destroying cartilage. This suggests that they could be used in targeted therapies—new strategies that are developed to block their activity may actually prevent damage," says Dr. Kapoor.
Next, the team will investigate whether these new biomarkers can be detected in the blood and their utility as an early detection test: if they are present in the blood when early or mild symptoms arise, then clinicians will know to prescribe treatments that can help prevent significant damage before it begins. The researchers will also test if blocking these biomarkers can halt spine degeneration.
This work was supported by the University Health Network Arthritis Program, the Krembil Foundation and the Toronto General & Western Hospital Foundation. I Jurisica is a Tier 1 Canada Research Chair in Integrative Cancer Informatics.
Identification of microRNA-181a-5p and microRNA-4454 as mediators of facet cartilage degeneration. Nakamura A, Rampersaud YR, Sharma A, Lewis SJ, Wu B, Datta P, Sundararajan K, Endisha H, Rossomacha E, Rockel JS, Jurisica I, Kapoor M. Journal of Clinical Investigation Insight. doi:10.1172/jci.insight.86820.I. [Manuscript link]
A team led by Krembil Senior Scientist Dr. Mohit Kapoor, including postdoctoral fellow Dr. Akihiro Nakamura and Krembil Clinician Investigator Dr. Y. Raja Rampersaud, recently analyzed tissue biopsies from 55 patients with spine OA. They screened 2,100 biological molecules known as microRNAs and found that two of these—microRNA-181a-5p and microRNA-4454—may be able to help clinicians determine the severity of spine OA. The study also revealed that elevated levels of these biomarkers may actually be involved in the underlying mechanisms leading to inflammation, cartilage destruction and collagen depletion.
"The most critical aspect of this discovery is that we have found that these two molecules are actively involved in increasing inflammation and destroying cartilage. This suggests that they could be used in targeted therapies—new strategies that are developed to block their activity may actually prevent damage," says Dr. Kapoor.
Next, the team will investigate whether these new biomarkers can be detected in the blood and their utility as an early detection test: if they are present in the blood when early or mild symptoms arise, then clinicians will know to prescribe treatments that can help prevent significant damage before it begins. The researchers will also test if blocking these biomarkers can halt spine degeneration.
This work was supported by the University Health Network Arthritis Program, the Krembil Foundation and the Toronto General & Western Hospital Foundation. I Jurisica is a Tier 1 Canada Research Chair in Integrative Cancer Informatics.
Identification of microRNA-181a-5p and microRNA-4454 as mediators of facet cartilage degeneration. Nakamura A, Rampersaud YR, Sharma A, Lewis SJ, Wu B, Datta P, Sundararajan K, Endisha H, Rossomacha E, Rockel JS, Jurisica I, Kapoor M. Journal of Clinical Investigation Insight. doi:10.1172/jci.insight.86820.I. [Manuscript link]