Senescent mesenchymal stem cells (hMSCs) are found in cartilage tissues isolated fromosteoarthritis patients suggesting a role of these cells in the disease. A joint research group of CAS Institute of Zoology, Institute of Biophysics and Peking University have now found in animal experiments that a protein, CBX4, protected hMSCs against cellular senescence through the regulation of nucleolar architecture and function. CBX4 protein was downregulated in aged hMSCs whereas CBX4 knockout in hMSCs resulted in destabilized nucleolar heterochromatin, enhanced ribosome biogenesis, increased protein translation, and accelerated cellular senescence. The researchers conclude that CBX4 maintains nucleolar homeostasis by recruiting nucleolar protein fibrillarin and heterochromatin protein KRAB-associated protein 1 (KAP1) at nucleolar rDNA, limiting the excessive expression of rRNAs.When CBX4 was overexpressed in mice, the development of osteoarthritis could be attenuated. This suggests that gene therapy might be a future therapy for the alleviation of osteoarthritis in man.

CAS news release, March 26, 2019