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UNCOVERING THE BY TIFFANY PARNELL THE MOST COMMON form of arthritis, OA a¢ects about 31 million adults, according to the CDC. The disease causes significant pain and joint inflammation and is a leading cause of disability and healthcare expenditure in aging populations. OA occurs when the articular cartilage that covers the bony surfaces within a joint begins to break down. The exact mechanisms responsible for OA development are unknown, but mechanical wear and tear and biological changes within the joint are both suspected of playing roles, according to Claudette Lajam, MD, orthopedic surgeon at NYU Langone Orthopedics. A review published in Best Practices & Research Clinical Rheumatology reports that age is the "single greatest risk factor for the development of OA." Other risk factors include obesity, a history of joint injury and genetic predisposition. THE CELLULAR SENESCENCE-OA CONNECTION With increasing age comes a greater accumulation of senescent cells. Those cells have undergone cell fate decision, no longer divide, are largely resistant to cell death, and produce a variety of inflammatory mediators that cause local inflammation and contribute to the deterioration of the extracellular matrix in cartilage and bone. Factors driving cellular senescence include potentially cancerous cell insults, such as DNA damage and the shortening of telomeres at the ends of chromosomes, as well as metabolic insults such as high blood glucose levels, says James Kirkland, MD, PhD, Director of the Robert and Arlene Kogod Center on Aging at the Mayo Clinic and senior author of the research study. "These cells have been noted to accumulate around tissues in histological sections of joints from people who've had osteoarthritis and have a knee or hip replacement ...," Dr. Kirkland says. "Whether they are a cause or an e¢ect or an incidental finding with respect to osteoarthritis hasn't been shown before. What we set out to do was show whether senescent cells in and of themselves could promote or cause the development of an osteoarthritis-like state. If so, that would argue that they contribute to the etiology and be one of the things that ties predisposition to osteoarthritis with chronological aging." INVESTIGATIONAL HIGHLIGHTS To explore the potential causal relationship between senescent cells and OA development, the research team injected 100,000 senescent or nonsenescent cells into and around the knee joints of mice, which rarely develop age-related OA. Cells used in the study were fibroblasts harvested from each animal's ear cartilage. To induce cellular senescence, the A CAUSAL REL ATIONSHIP E XISTS BE T WEEN SENESCENT CELLS AND OSTEOARTHRITIS ¢OA£ DE VELOPMENT, ACCORDING TO A RECENT STUDY IN THE JOURNALS OF GERONTOLOGY SERIES A: BIOLOGICAL SCIENCES AND MEDICAL SCIENCES. THAT FINDING CONFIRMS WHAT RESE ARCHERS HAVE LONG SUSPECTED. 1 4