Sunday , June 20 2021

Absence of a key protein can lead to rapid, severe bone loss

The absence of a protein that is critical to control inflammation can lead to a rapid and severe loss of bone mass, according to a new university study in Buffalo.

The study found that when the gene required for the production of protein triestetrarolin (TTP) was removed from healthy mice, the animals developed the bones of many older rodents.

Within nine months, mice without a gene experienced a loss of about 20 per cent in the oral bone. The results also showed that overexpression of TTP in animals led to a 13 percent decrease in bone turnover compared to unchanged mice.

Posted on March 7 in the Journal of Dental Research, the study is the first to test the effects of TTP on bone loss in the animal model.

Inflammation is a necessary response from the immune system to protect the body from injury or infection, but if it is not controlled, it can lead to bone destruction and prevent the formation of bones.

Although it is known that TTP plays a major role in regulation of inflammation, its production slows down with age. The results of the research could have a major impact on the management of bone health in the elderly, the population at higher risk of osteoporosis and periodontitis.

"TTP is a brake on the system, without it, inflammation and bone loss will not be controlled," said Keith Kirkwood, DDS, PhD, chief author and professor at the Department of Oral Biology at the UB School of Dental Medicine.

"We do not know all the reasons why TTP expression decreases with age," he said. "The understanding of the factors behind his expression and the relationship with bone loss is the first step towards designing therapeutic approaches."

The researchers aim to advance their investigation into similar studies in humans, especially in aging.

Osteoporosis, a condition in which bones become weak and brittle, and low bone mass affects almost 55 per cent of people aged 50 years and older, and it is estimated that by 2020, more than 61 million people will have either a condition, says the National Foundation for osteoporosis.

The statistics about periodontitis are equally gloomy. Infection – which damages the gums, destroys the bone of the jaw and can lead to tooth loss – occurs in 70 per cent of adults aged 65 years and older, according to the Centers for Disease Control and Prevention.

To better understand the role of TTP in periodontitis, an inflammatory disease, the researchers studied three groups of healthy mice: a knockout group without a gene to express a TTP, a shock group whose genes exceeded TTP and a control group of unchanged mice.

Rodents have been tested for inflammatory conditions, oral bone levels and the presence of osteoclasts – cells that specialize in bone breakdown – in oral tissue for a period of three, six, and nine months.

The researchers found that bone in knockout mice was older than faster than in the control group. At the age of three months, mice lost 14 percent of their oral bone. Since nine months – another young age for bone density loss has increased to 19 percent.

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

Investigators were surprised when they discovered that the absence of TTP significantly altered the oral microbial, even though all rodents were located in the same space. This finding suggests that systematic inflammation may affect the bacteria in the mouth. Further research is needed to determine if new bacteria are pathogenic or play a role in bone loss, says Kirkwood.

Excessive expression of TTP in rats with mice increased the protection against inflammation, reducing bone turnover by 13 per cent. However, the increase in protein did not affect the number of osteoclasts.

A future investigation will study the effect of TTP on bone health over a period of two years. Kirkwood will also collaborate with Dr. Bruce Troen, MD, professor and Dr. Kenneth Selden, PhD, research assistant at the Jacobs School of Medicine and Biomedical Science, to investigate the differences in the impact of proteins on the oral bone and the overall bone health.

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