Navigation Links
Researchers identify protein involved in causing gum disease, osteoporosis, arthritis
Date:8/30/2009

Investigators at Hospital for Special Surgery, collaborating with researchers from other institutions, have contributed to the discovery that a gene called interferon regulator factor-8 (IRF-8) is involved in the development of diseases such as periodontitis (gum disease), rheumatoid arthritis and osteoporosis. The study, which will be published online August 30, ahead of print, in the journal Nature Medicine, could lead to new treatments in the future.

"The study doesn't have immediate therapeutic applications, but it does open a new avenue of research that could help identify novel therapeutic approaches or interventions to treat diseases such as periodontitis, rheumatoid arthritis or osteoporosis," said Baohong Zhao, Ph.D., lead author of the study and a research fellow in the Arthritis and Tissue Degeneration Program at Hospital for Special Surgery located in New York City.

Dr. Zhao initiated the study while working in the laboratory led by Drs. Masamichi Takami and Ryutaro Kamijo at Showa University, Tokyo, where much of the work was performed. Dr. Zhao completed the study and extended the work to human cells during the past year at Hospital for Special Surgery working with Dr. Lionel Ivashkiv.

Specifically, the researchers discovered that downregulation of IRF-8 (meaning that the gene produces less IRF-8 protein) increases the production of cells called osteoclasts that are responsible for breaking down bone. An osteoblast is a type of cell that is responsible for forming bone and an osteoclast is a type of cell that breaks down bony tissue (bone resorption). In humans and animals, bone formation and bone resorption are closely coupled processes involved in the normal remodeling of bone. Enhanced development of osteoclasts, however, can create canals and cavities that are hallmarks of diseases such as periodontitis, osteoporosis and rheumatoid arthritis.

Previous researchers have spent time identifying genes that are upregulated during enhanced development of osteoclasts, such as NFATc1, but few studies have identified genes that are downregulated in the process. To fill this knowledge gap, scientists at Hospital for Special Surgery, collaborating with researchers at other institutions, used microarray technology to conduct a genome-wide screen to identify genes that are downregulated during the formation of osteoclasts. They found that expression of IRF-8 was reduced by 75 percent in the initial phases of osteoclast development.

The researchers then genetically engineered mice to be deficient in IRF-8 and gave the animals x-rays and CT (computed tomography) scans to analyze IRF-8's influence on bone. They found that the mice had decreased bone mass and severe osteoporosis. Experiments demonstrated that this was due not to a decreased number of osteoblasts, but because of an increased number of osteoclasts. The researchers concluded that IRF-8 suppresses the production of osteoclasts.

Tests in human cells confirmed these findings. This included a study that showed that silencing IRF-8 messenger RNA in human osteoclast precursors with small interfering RNAs resulted in enhanced osteoclast production. In other words, decreased IRF-8 means more osteoclasts are produced.

This led the investigators to examine the effect of IRF-8 on the activity of a protein called NFATc1 that was previously reported to interact with IRF-8. They found that IRF-8 inhibited the function and expression of NFATc1. This makes sense given that upregulation of NFATc1 is involved in triggering osteoclast precursor cells to turn into osteoclasts.

"This is the first paper to identify that IRF-8 is a novel key inhibitory factor in osteoclastogenesis [production of osteoclasts]," said Dr. Zhao. "We hope that the understanding of this gene can contribute to understanding the regulatory network of osteoclastogenesis and lead to new therapeutic approaches in the future."


'/>"/>

Contact: Phyllis Fisher
fisherp@hss.edu
212-606-1197
Hospital for Special Surgery
Source:Eurekalert

Related medicine news :

1. Stanford researchers find culprit in aging muscles that heal poorly
2. UCLA researchers identify markers that may predict diabetes in still-healthy people
3. Mayo Clinic researchers discover new diagnostic test for detecting infection in prosthetic joints
4. Bipolar disorder relapses halved by Melbourne researchers
5. Cell that triggers symptoms in allergy attacks can also limit damage, Stanford researchers find
6. High and mighty: first common height gene identified by researchers behind obesity gene finding
7. Researchers estimate about 9 percent of US children age 8 to 15 meet criteria for having ADHD
8. Majority of 2.4 Million U.S. Children With ADHD Not Diagnosed or Consistently Treated, According to New Gold Standard Study by Cincinnati Childrens Researchers
9. Researchers develop long-lasting growth hormone
10. Jefferson immunology researchers halt lethal rabies infection in brain
11. Purdue researchers develop technology to detect cancer by scanning surface veins
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:12/2/2016)... ... December 02, 2016 , ... Sourced from the Isbre ... unique properties including its unmatched natural purity of just 6 ppm TDS (Total Dissolved ... , Nothing Water has been available in several ShopRite and FoodTown stores in NJ ...
(Date:12/2/2016)... ... December 02, 2016 , ... Clarify ... it has raised $6.0 million in an initial round of funding. The round ... patients and their caregivers can receive far better care through the application of ...
(Date:12/2/2016)... , ... December 02, 2016 , ... ‘Tis the season ... of $1,000 each from the National Family Partnership and the Drug Enforcement Administration as ... decorated their homes and the 10 winning schools who decorated their campuses with this ...
(Date:11/30/2016)... ... November 30, 2016 , ... Standard Process, Inc. is proud ... and recognition of the largest closely held companies headquartered in Wisconsin. This marks ... addition, Standard Process was awarded the Talent Award for providing outstanding employee benefits. ...
(Date:11/30/2016)... ... November 30, 2016 , ... ... and stylish design wanted by today’s consumers at an affordable price, is now ... says the new watch is “a game changer” when it comes to the ...
Breaking Medicine News(10 mins):
(Date:12/2/2016)... , Dec. 2, 2016 Lianluo Smart ... or "the Company") which develops, markets and sells ... China and international markets, ... Diagnosis and Treatment New Progress Forum, co-hosted by ... Guangdong Province , Guangdong Provincial People,s Hospital ...
(Date:12/2/2016)... -- On Thursday, the NASDAQ Composite ended the ... Average edged 0.36% higher, to finish at 19,191.93; and the ... based as six out of nine sectors ended the day ... following Services equities: Myriad Genetics Inc. (NASDAQ: MYGN ... Holdings Inc. (NASDAQ: INCR ), and La Quinta ...
(Date:12/2/2016)... , Dec. 1, 2016  Today, Simpson Healthcare ... the honor of being selected as winners of multiple ... Healthcare Executives Website at the PLATINUM level, Blue Zones ... Module at the GOLD Level, and our proprietary 3ConneX ... At Simpson Healthcare Executives, we are excited to showcase ...
Breaking Medicine Technology: