A research group at Hokkaido University has revealed that "inflammatory amplifiers" present in chondrocytes are involved in the development of arthritis.
There are still intractable cases of "rheumatoid arthritis" in which joints become inflamed and then deformed, and "osteoarthritis" in which cartilage is destroyed or changed with chronic inflammation, even though treatment methods have advanced. , It is a disease that is difficult to cure completely.
Therefore, in this study, we focused on chondrocytes, which have not received much attention so far.In previous studies, the researchers reported the mechanism that causes chronic inflammation, the "inflammatory amplifier," and said that they conducted research on the assumption that an inflammatory amplifier exists in chondrocytes and is involved in the development of arthritis.
As a result, it was clarified that the mechanism of inflammatory amplifier exists in chondrocytes of rheumatoid arthritis and osteoarthritis.In the inflammation amplifier, the transcription factors NF-κB and STAT3 are activated at the same time, and various inflammatory cytokines, chemokines, growth factors, etc. are produced in large quantities, so that immune cells are locally accumulated and inflammation is induced. NS.In chondrocytes, activation of NF-κB and STAT3, which are indicators of inflammatory amplifier activation, was also observed.It was also found that specific suppression of chondrocyte inflammatory amplifiers suppresses arthritis in arthritis model mice.
Furthermore, it was also found that TMEM147, which was identified as one of the genes related to inflammation amplifiers, is strongly expressed in chondrocytes of arthritis.Overexpression of TMEM147 in chondrocyte lines enhanced the NF-κB pathway of the inflammatory amplifier, demonstrating that TMEM147 positively controls the inflammatory amplifier.
On the contrary, it was found that suppression of the TMEM147 gene or addition of anti-TMEM147 antibody suppressed the activation of the inflammatory amplifier and significantly suppressed arthritis, and the anti-TMEM147 antibody had a therapeutic effect on the arthritis model. The possibility of having it was also shown.
This result is expected to contribute to the development of new treatments for rheumatoid arthritis and osteoarthritis.
Paper information:[Arthritis & Rheumatology] Chondrocytes play a role in the development of rheumatoid arthritis via TMEM147-mediated NF-κB activation
