A new study by experts at the Hospital for Special Surgery claims that a gene known as interferon regulator factor-8 (IRF-8) is supposedly involved in the development of diseases such as periodontitis (gum disease), rheumatoid arthritis and osteoporosis.
Dr. Zhao commenced the analysis 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 finished the study and extended the work to human cells during the past year at Hospital for Special surgery working with Dr. Lionel Ivashkiv.
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 commented “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.”
The production of cells known as osteoclasts that are accountable for breaking down a bone were supposedly increased by the downregulation of IRF-8. An osteoblast is a kind of cell that may be in charge of bone formation and an osteoclast is a type of cell that supposedly breaks down bony tissue (bone resorption). Bone formation and bone resorption are intimately coupled processes which could be involved in the normal remodeling of bone in both animals as well as humans. Improved development of osteoclasts may create canals and cavities that are supposedly the trademark for diseases like periodontitis, osteoporosis and rheumatoid arthritis.
Preceding experts have spent time detecting genes that seemed to be unregulated during improved development of osteoclasts, such as NFATc1, but only some studies have recognized genes that are downregulated in the process. A microarray technology to carry out a genome-wide screen to identify genes that are apparently downregulated during the formation of osteoclasts was used by the scientists at Hospital for Special Surgery with experts at other institutions. It was seen that the expression of IRF-8 was supposedly decreased by 75 percent in the early stage of osteoclast development.
The study experts genetically engineered the mice to be deficient in IRF-8 and the animals underwent x-rays and CT (computed tomography) scans to investigate IRF-8’s influence on the bone. It was apparently seen that the mice had reduced bone mass and severe osteoporosis. Experiments illustrated that this was due to a rising number of osteoclasts and not because of a decreased number of osteoblasts. The experts deduced that IRF-8 apparently curbs the production of osteoclasts.
These findings are apparently verified by the tests in human cells. This included a study that demonstrated the silencing IRF-8 messenger RNA in human osteoclast forerunners with small interfering RNAs could lead to improved osteoclast production. In simple terms, reduced IRF-8 could mean that more osteoclasts are produced.
This apparently led the investigators to inspect the effect of IRF-8 on the movement of a protein known as NFATc1 that was earlier reported to communicate with IRF-8. They discovered that IRF-8 repressed the function and expression of NFATc1. According to the experts, this makes sense as upregulation of NFATc1could be implicated in activating osteoclast precursor cells to turn into osteoclasts.
Dr. Zhao commented that this is the first paper to identify that IRF-8 is a novel key inhibitory factor in osteoclastogenesis which is cliamed to be the production of osteoclasts. The scientists 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.
This study was published in the journal Nature Medicine.