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 1. Home
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 3. NIDCR News
 4. NIDCR News 2022
 5. Tooth Protein Prevents Bone Loss in Mice

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TOOTH PROTEIN PREVENTS BONE LOSS IN MICE

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SCIENTISTS REVEAL SURPRISING VERSATILITY OF ENAMEL-RELATED PROTEIN

IN BRIEF:

 * NIDCR scientists and colleagues found that a tooth-hardening protein can also
   help prevent bone loss in mice.
 * The protein could have therapeutic potential for conditions marked by bone
   loss, including severe gum disease and osteoporosis.

What is the hardest tissue in the human body? It’s not our bones. It’s enamel,
the pearly white tissue that coats and protects our teeth. Enamel is formed with
the help of proteins called amelogenins. But as a recent study shows, these
proteins appear to do more than fortify our teeth—they may also help keep our
bones strong.


Ashok Kulkarni and colleagues revealed a small tooth protein’s role in promoting
bone growth and preventing bone loss, which may have implications for conditions
marked by bone loss, such as periodontitis. | NIDCR

A research team led by NIDCR senior investigator Ashok Kulkarni, PhD, found that
a small enamel protein called leucine-rich amelogenin peptide (LRAP) can promote
bone formation and prevent bone loss in mice. The results, published in the
journal PLoS One, suggest potential interventions for conditions marked by bone
loss, such as advanced gum disease and osteoporosis.

Since LRAP’s identification in 1991 by study co-author and long-time
collaborator Carolyn Gibson, PhD, at the University of Pennsylvania, scientists
have wondered what it does. “It was like solving a big puzzle,” says Kulkarni.
“Now we know this protein that is synthesized in the teeth has a role in bone
turnover, which is one of the most important processes for bone regeneration.”
Kulkarni credits first author and former research fellow Naoto Haruyama, DDS,
PhD, for spearheading the study. Haruyama is now an associate professor at
Kyushu University, Japan.

To drill down on LRAP’s role beyond teeth, the team engineered mice that
produced high levels of LRAP and compared them to normal mice. On a petri dish
under the microscope, the skull tissue of engineered mice showed increased
activity of bone-generating cells, calcium accumulation, and a decrease in cells
that break down bone—all hallmarks of LRAP’s involvement in bone turnover. This
process, where worn out bone is continually replaced by new tissue, occurs
throughout our lives to keep bones strong, and it helps to repair micro cracks
that can accrue from daily activities, as well as larger fractures from
injuries.

Aside from these microscopic differences, though, the bones from the two groups
of mice appeared similar. “That changed when we stressed the bones, and the
difference was striking,” says Kulkarni.


When the researchers simulated menopause in mice, bone from mice with excess
LRAP (right) was thicker and denser than bone from the mice with normal levels
of LRAP (left), as shown in these 3D models. | Ashok Kulkarni

To do so, the scientists simulated menopause in both groups of mice to mimic the
bone loss that often occurs in humans after menopause. As expected, normal mice
experienced rapid bone loss in their legs. X-rays and 3D bone scans also showed
that their bones were thinner and hollower. However, mice with excess LRAP
withstood these effects. Instead, their bones resembled those of healthy mice
who had not undergone simulated menopause. The results are the first to show
that LRAP affects bone turnover in living animals.

The findings suggest that LRAP could have therapeutic potential for conditions
that cause bone loss. Next, the team plans to test whether LRAP can prevent bone
loss in mice with periodontitis, a severe form of gum disease that can degrade
the bone that supports the teeth. Kulkarni is optimistic about the possibility.
An experimental compound rich in proteins similar to LRAP has been tested by
other investigators in patients with periodontitis-induced bone loss and was
reported to regenerate some bone tissue in the oral cavity.

“I think there are certainly implications that LRAP may have therapeutic value
in preventing bone loss,” says Kulkarni. “But we still have a long way to go
before the research could be applied to humans.”


RELATED LINKS

 * Turning Back the Clock on Gum Disease
 * Complexity of Human Tooth Enamel Revealed at Atomic Level
 * Scientists Take a Crack at Bone Regeneration
 * Researchers Identify Immune Culprits Linked to Inflammation and Bone Loss in
   Gum Disease

Reference

Leucine rich amelogenin peptide prevents ovariectomy-induced bone loss in mice.
Haruyama N, Yamaza T, Suzuki S, Hall B, Cho A, Gibson CW, Kulkarni AB. PLoS One.
2021 Nov 15;16(11):e0259966. doi: 10.1371/journal.pone.0259966. PMID: 34780561;
PMCID: PMC8592471.


ATTENTION EDITORS

Reprint this article in your own publication or post to your website. NIDCR News
articles are not copyrighted. Please acknowledge NIH's National Institute of
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