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Large Joints Feature

Senescence on mouse embryonic fibroblast cells. Upper: Before senescence, at 2nd (early) passage. Lower: After senescence, at 8th (late) passage. ; Source: Wikimedia Commons and Y tambe

Old Cells: Get Them Out and Stop OA

Elizabeth Hofheinz, M.P.H., M.Ed. • Tue, May 9th, 2017

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Researchers from Korea, the Netherlands, and the U.S. have explored what happens to joints when old (senescent) cells are cleared out. Using mice and human cells, researchers found that post-traumatic osteoarthritis (OA) was reduced.

The April 26, 2017 Johns Hopkins Medicine news release states, “Senescent cells accumulate in tissues as we age and are a normal part of wound healing and injury repair. They secrete important signals that call immune cells and other cell types into damaged tissue so they can clean up and rebuild. However, in articular joints such as the knee, and cartilage tissue in particular, these senescent cells often are not cleared from the area after injury. Their prolonged presence causes a cascade of events, which starts the development of osteoarthritis.”

The study, published online April 24, 2017 in Nature Medicine, was entitled, “Local clearance of senescent cells attenuates the development of post-traumatic osteoarthritis and creates a pro-regenerative environment.”

Jennifer Elisseeff, Ph.D., director of the translational tissue engineering center and Morton Goldberg Professor of Ophthalmology at the Johns Hopkins Wilmer Eye Institute, co-author on the study told OTW, “There has been an exciting wealth of new research in the area of senescent cells and aging. Combine this with the findings of senescent cells in tissue isolated from patients undergoing TKA [total knee arthroplasty] and it was an exciting project to explore.”

According to the description of the study released by Johns Hopkins, “The researchers took young mice and performed surgery on them, cutting their anterior cruciate ligaments (ACL) to mimic injury. The researchers then administered injections of an experimental drug named UBX0101…and observed that the presence of senescent cells was reduced by roughly 5%. In addition, the researchers monitored gene expression in treated mice and found that genes associated with reparative cartilage growth were activated in the joint after treatment.”

"What was most striking about the results in human tissue is the fact that removal of senescent cells had a profound effect on tissue from very advanced osteoarthritis patients, suggesting that even patients with advanced disease could benefit," said Dr. Elisseeff.

Dr. Elisseeff told OTW, “What I like about this study design is that it includes transgenic animals where we could closely look at the biological mechanisms, normal animals and finally cells from human tissue. Clearing senescent cells reduces post-traumatic OA (that could be instigated by simple arthroscopies) and age-related disease. We were surprised about the differences in older animals; we are pursuing this and already finding exciting results.”

“OA is not just a mechanical disease and the interesting biology in the joint will be critical for optimally treating patients."

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