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:2/18/2017)... ... February 17, 2017 , ... Focused start-ups, not ... the industry, according to the recent NEJM Catalyst Insights Report on the New ... NEJM Catalyst Insights Council, a qualified group of U.S. executives, clinical leaders, and ...
(Date:2/18/2017)... ... February 18, 2017 , ... ProParagraph Fashion Volume 2 features ... ProParagraph Fashion Volume 2 for all multi-line FCPX project needs. Great for ... and choose from hand-crafted trend-setting designs with smooth animations that will add stylistic ...
(Date:2/17/2017)... ... February 17, 2017 , ... The Alliance ... change designed to further positively impact the health and wellness of our community ... considered it our duty to seriously consider releasing our assets beyond our 5% ...
(Date:2/17/2017)... ... February 17, 2017 , ... Empowering ... Francis' goals for each and every seminar, session and class she offers. ... five different brainwave tools which help energize creativity, focus mental functions, enhance athletic ...
(Date:2/17/2017)... WASHINGTON (PRWEB) , ... February 17, 2017 , ... ... communities by fall 2017 season , Trinity Health and the U.S. Soccer Foundation ... for Success program in underserved communities. Soccer for Success, the Foundation’s soccer mentoring ...
Breaking Medicine News(10 mins):
(Date:2/17/2017)... 17, 2017 Research and Markets has announced the ... report to their offering. ... The report provides separate comprehensive analytics for the US, Canada ... Asia-Pacific , and Rest of World. Annual estimates and ... historic analysis is provided for these markets. Market data and analytics are ...
(Date:2/17/2017)... ST. LOUIS , Feb. 17, 2017   ... hospitals, has announced a new partnership with Engage ... the United States . FormFast will serve ... part of Engage,s implementations with MEDITECH .  ... that provides essential functionality to complement and enhance the ...
(Date:2/17/2017)... NEW YORK , Feb. 17, 2017  Noble ... coverage on ESSA Pharma Inc. (Nasdaq: EPIX ... Biotechnology Research, Kumar Raja , PhD. ... treatments for castration resistant prostate cancer (CRPC). Its lead ... selectively blocks the amino-terminal domain of the androgen receptor, ...
Breaking Medicine Technology: