The AtoMs
Newly discovered cell involved in rheumatoid arthritis could serve as treatment target
https://www.news-medical.net/news/20191118/Newly-discovered-cell-involved-in-rheumatoid-arthritis-could-serve-as-treatment-target.aspx NATURE Immunology Nov. 18, 2019
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Researchers at Osaka University in Japan have made an important discovery about a class of cells involved in rheumatoid arthritis (RA) that could pave the way for new treatments. The team discovered a NEW SUBTYPE of osteoclasts within affected joints that could serve as a potentially therapeutic target.
ARTHRITIS refers to a group of more than 100 chronic diseases characterized by inflammation in the joints that can eventually lead to irreparable damage and debilitating pain and stiffness. Rheumatoid arthritis is an autoimmune form of the disease, where immune cells mistakenly target tissue that lines the joints, causing pain, swelling, and stiffness. Over time, this can damage the joints, cartilage, and surrounding bone.
There is currently no cure for RA, and treatment approaches are limited to drugs to alleviate symptoms or at best delay disease progression, thus scientists are researching the condition in efforts to find potential new treatment targets.
In RA, two main CELL TYPES contribute to the disease progression. Firstly, immune cells release inflammatory cytokines that aggravate tissue lining the joints. Secondly, specialized cells called osteoclasts secrete enzymes and acids that "dissolve" bone.
In a healthy, non-disease state, osteoclasts remodel the bone, but in RA, their ability to breakdown bone is ramped up, which damages joints instead.
Currently, treatments for RA mainly target the immune cells. Treatments that target osteoclasts are limited because we do not know enough about how they are involved in RA. Understanding how these cells are different from the osteoclasts involved in normal physiological processes is persuasive.
Osteoclasts usually line the bone surface underneath layers of cartilage and tissue, which makes them difficult to isolate. A NEW TECHNIQUE for isolating osteoclasts was introduced by the team.
While normal osteoclasts are derived from stem cells in the bone marrow, osteoclasts involved in RA come from blood-borne precursors. The circulating precursors enter the joint and differentiate into a unique sub-type of osteoclasts, which are larger and have distinct markers that are not seen in other osteoclasts !
The NEW SUBTYPE of osteoclasts had properties that could be manipulated: The newly found cells, which the team has dubbed "AtoMs" (Arthritis-associated osteoclastogenic Macrophages), possess properties that could be manipulated in approaches to developing new treatments. For example, the AtoMs have an abundance of the protein FoxM1, which is known to make cells invade tissue. The team hypothesized that eliminating this protein may reduce its arthritis-inducing ability. As reported in "Nature Immunology" the researchers confirmed that this was, in fact, the case. When they genetically or chemically disabled FoxM1 in AtoMs, the destruction of the bone was reduced in the animals' joints.
OSTEOCLASTS IN RA HAVE DISTINCT PROPERTIES THAT MAKE THEM AMENABLE TO THERAPEUTIC TARGETING
THERE IS STILL A LOT TO LEARN ABOUT THIS CLASS OF CELLS, YET THE DISCOVERY COULD OPEN DOOR TO NEW AVENUES OF TREATMENT
Source: Researchers split the 'AtoM' in search of a treatment for rheumatoid arthritis. Eurekalert. Available at: https://www.eurekalert.org/emb_rel…/2019-11/ou-rst111219.php
Great read! I wonder when we would see the face of this drug being used in humans
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