Study: Absence of key protein, TTP, rapidly turns young bones old

March 10, 2018 by Marcene Robinson, University at Buffalo
The removal of the gene that produces TTP progressively increases the presence of osteoclasts (red) -- cells that break down and absorb bone -- causing rapid bone loss in mice (middle) compared with healthy mice (left). Credit: Keith Kirkwood

The absence of a protein critical to the control of inflammation may lead to rapid and severe bone loss, according to a new University at Buffalo study.

The study found that when the gene needed to produce the protein tristetraprolin (TTP) is removed from healthy , the animals developed the bones of much older rodents.

Within nine months, mice without the gene experienced a nearly 20 percent loss in oral bone. The results also revealed that overexpressing TTP in the animals led to a 13 percent reduction in bone turnover compared to unaffected mice.

Published on March 7 in the Journal of Dental Research, the study is the first to test TTP's influence on in an animal model.

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 .

While TTP is known to play a major role in the regulation of inflammation, its production slows with age. The research results could have a profound impact on the management of in the elderly, a population at higher risk of osteoporosis and periodontitis.

"TTP is the brake on the system. Without it, inflammation and bone loss would go unchecked," says Keith Kirkwood, DDS, PhD, lead author and professor in the Department of Oral Biology in UB's School of Dental Medicine.

"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."

The researchers aim to advance their investigation toward similar studies in humans, particularly among the aging.

Osteoporosis, a condition in which bones become weak and brittle, and low bone mass affect nearly 55 percent of people age 50 and older, and it is estimated that by 2020, more than 61 million people will have either condition, the National Osteoporosis Foundation says.

The statistics surrounding periodontitis are equally grim. The infection - which damages the gums, destroys and can lead to tooth loss - occurs in 70 percent of adults age 65 and older, according to the Centers for Disease Control and Prevention.

To better understand TTP's role in periodontitis, an inflammatory disease, the researchers 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.

The rodents were tested for inflammatory conditions, oral bone levels and the presence of osteoclasts - cells that specialize in breaking down bone - in oral tissue at three-, six- and nine-month periods.

The researchers found that bone in the knockout mice aged more rapidly than in the control group. At three months old, the mice had lost 14 percent of their oral bone. By nine months - still a young age for a mouse - bone loss had increased to 19 percent.

In addition to periodontitis, the knockout mice developed arthritis, eczema and other inflammatory conditions. Osteoclast levels were also higher in the knockout group.

Investigators were surprised to find that the absence of TTP vastly altered the oral microbiome, despite all the rodents being housed in the same space. The finding suggests that systematic inflammation can affect the bacteria in the mouth. Further study is needed to determine whether the new bacteria are pathogenic or play a role in bone loss, says Kirkwood.

Overexpression of TTP in the knock-in mice increased protection against inflammation, lowering bone turnover by 13 percent. The increase in the protein had no effect on the number of osteoclasts, however.

A future investigation will study the effect of TTP on bone health over a two-year period. Kirkwood will also partner with Bruce Troen, MD, professor, and Kenneth Seldeen, PhD, research assistant professor, both in the Jacobs School of Medicine and Biomedical Sciences, to examine the differences in the protein's influence on oral bone and overall health.

Explore further: Muscle paralysis may increase bone loss

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

Related Stories

Muscle paralysis may increase bone loss

December 15, 2017
Muscle paralysis rapidly causes inflammation in nearby bone marrow, which may promote the formation of large cells that break down bone, a new study finds. The article is published in the American Journal of Physiology—Cell ...

Reversing severe bone loss

February 7, 2018
A possible first-line treatment for a rare bone loss disease has been identified by a research team led by Tohoku University in Japan. The research findings, published in the journal Molecular Cell, could also provide insight ...

Probiotics protect mice from estrogen deficiency-related bone loss

April 25, 2016
After menopause, a decline in estrogen levels is linked to increases in inflammation that can cause osteoporosis. Intestinal bacteria have been shown to influence inflammation by modulating immune responses, and a new study ...

Researchers discover gene that slows bone loss and promotes bone formation

August 12, 2014
(Medical Xpress)—Osteoporosis and aging-related bone loss is debilitating and painful. With a greater understanding of Wnt4 signaling, researchers are now closer to developing therapeutic agents that could slow down bone ...

Diabetes causes shift in oral microbiome that fosters periodontitis, study finds

July 12, 2017
A new study led by University of Pennsylvania researchers has found that the oral microbiome is affected by diabetes, causing a shift to increase its pathogenicity. The research, published in the journal Cell Host & Microbe ...

Identification of a molecule linking bone loss and bone formation

August 1, 2013
Bone integrity requires skeletal remodeling, which involves both bone formation and resorption. It has been previously shown that the formation of new bone is triggered by degradation of older bone. However, it is unknown ...

Recommended for you

Researchers discover cellular messengers communicate with bacteria in the mouth

May 8, 2018
A new UCLA-led study provides clear evidence that cellular messengers in saliva may be able to regulate the growth of oral bacteria responsible for diseases, such as periodontitis and meningitis.

Drug-filled, 3-D printed dentures could fight off infections

April 25, 2018
Nearly two-thirds of the U.S. denture-wearing population suffer frequent fungal infections that cause inflammation, redness and swelling in the mouth.

Bacteria boost antifungal drug resistance in severe childhood tooth decay

April 25, 2018
Early childhood caries, a form of severe tooth decay affecting toddlers and preschoolers, can set children up for a lifetime of dental and health problems. The problem can be significant enough that surgery is the only effective ...

Absence of a transcription factor halts tooth development in mid-stride

April 11, 2018
Amjad Javed, Ph.D., and University of Alabama at Birmingham colleagues have found a key role in tooth development for the transcription factor Specificity protein 7, or Sp7.

Toothpaste alone does not prevent dental erosion or hypersensitivity

March 14, 2018
The rising prevalence of dental erosion and dentin hypersensitivity has led to the emergence of more toothpastes that claim to treat these problems. While no such toothpaste existed 20 years ago, today, many such brands are ...

Study: Absence of key protein, TTP, rapidly turns young bones old

March 10, 2018
The absence of a protein critical to the control of inflammation may lead to rapid and severe bone loss, according to a new University at Buffalo study.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.