Cell Rep: Chinese Academy of Sciences and Peking University cooperate to find a new target for the treatment of arthritis

March 31, 2019 / bioin / - aging is a risk factor of osteoarthritis (OA), which is a chronic disease characterized by pain and disability caused by degradation of articular cartilage Researchers have isolated senescent mesenchymal stem cells (hMSCs) from OA patients' joint tissues HMSCs is an important therapeutic target for tissue degradation Photo source: after four years of research, scientists from Institute of zoology, Chinese Academy of Sciences and Institute of Biophysics, Peking University reported their research results in cell reports They found that protein factor cbx4 can help treat OA in mice Scientists have found that cbx4 can protect hMSCs from aging by regulating nucleolar structure and function It is important that the overexpression of cbx4 can alleviate the development of OA in mice, which indicates that cbx4 is a therapeutic target that can be targeted for intervention Cbx4 is a component of core protein complex PRC1 (Polycomb reactive complex 1), which plays a key role in regulating cell identity and organ development through gene silencing Cbx4 in aging hMSCs is down regulated, while cbx4 knockout in hMSCs will lead to the instability of nucleolar heterochromatin, enhance the occurrence of ribosome organisms, increase protein translation, and accelerate cell aging Cbx4 limits the expression of excessive rRNAs by recruiting the nucleolar proteins, fibrinolytic protein and heterochromatin protein KRAB associated protein 1 (KAP1), into the nucleolar rDNA The overexpression of cbx4 can eliminate the physiological aging of hMSCs and slow down the development of OA in mice These findings not only emphasize the importance of cbx4 mediated nucleolar stability in preventing hMSCs from aging, but also provide a new method to prevent aging related stem cell failure, which is expected to be used in the treatment of aging related diseases Overall, the researchers revealed a new mechanism by which nucleolar protein cbx4 maintains the homeostasis of hMSC cells These findings prove that it is feasible to use gene therapy to restore the function of aging cells and treat OA, and provide a potential choice for future gerontology and regenerative medicine Reference: Xiaoqing Ren et al, maintenance of nuclear homestasis by cbx4 alleviates sense and osteoarthritis, cell reports (2019) Doi: 10.1016/j.celrep.2019.02.088