Study: Absence of Key Protein, TTP, Rapidly Turns Young Bones Old

Source: University of Buffalo

Summary: According to a new study, researchers found that the absence of a protein critical to the control of inflammation may lead to rapid and severe bone loss.

Osteoporosis, a condition in which bones become weak and brittle, and low bone mass affect nearly 55% of people age 50 and older, and it is estimated that by 2020, more than 61 million people will have either condition, according to the National Osteoporosis Foundation. The statistics surrounding periodontitis (an inflammatory disease) are equally grim. The infection which damages the gums, destroys jaw bone and can lead to tooth loss, occurs in 70% of adults age 65 and older, according to the Centers for Disease Control and Prevention. A new study by the researchers from the University of Buffalo found that the absence of a protein, tristetraprolin (TTP) critical to the control of inflammation may lead to rapid and severe bone loss. The study found that when the gene needed to produce the protein tristetraprolin (TTP) is removed from healthy mice, the animals developed the bones of much older rodents. The study findings were published in the journal Journal of Dental Research.

Protein which controls inflammation

The removal of the gene that produces TTP progressively increases the presence of osteoclasts (red) — cells that break down and absorb bone – causing a rapid bone loss in mice (middle) compared with healthy mice (left). Credit: Keith Kirkwood

Inflammation is a necessary reaction by the immune system to protect the body from injury or infection, but if not controlled, it can lead to the destruction of bone and the prevention of bone formation. To better understand TTP’s role in periodontitis, the research team studied three groups of healthy mice: a knockout group without the gene to express TTP, a knock-in group whose genes overexpressed TTP, and a control group of unaffected mice. They found that bone in the knockout mice aged more rapidly than in the control group. At 3 months old, the mice had lost 14% of their oral bone. By 9 months still a young age for a mouse – bone loss had increased to 19%. In addition to periodontitis, the knockout mice developed arthritis, eczema and other inflammatory conditions. Osteoclast levels were also higher in the knockout group. Overexpression of TTP in the knock-in mice increased protection against inflammation, lowering bone turnover by 13%.

Prof. Keith Kirkwood said, “TTP is the brake on the system. Without it, inflammation and bone loss would go unchecked”, “We don’t know all of the reasons why TTP expression decreases with age. So, understanding the factors behind its expression and relationship with bone loss is the first step toward designing therapeutic approaches.”

More Information: H.M. Steinkamp et al, “Tristetraprolin Is Required for Alveolar Bone Homeostasis”, Journal of Dental Research (2018). DOI: 10.1177/0022034518756889

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