Abstract
Aging is associated with an increased incidence of chronic degenerative diseases, including several joints diseases. Among them, Osteoarthritis is the most common. It is a complex degenerative joints discorder that causes pain and disability. in recent years, more and more evidences associate senescent cells accumulation to the development of osteoarthritis.We were interested in mesenchymal stem/stromal cells, the cells responsible for joint homeostasis maintenance. The alteration of their properties induced by senescence syndroma, defined as a "robust cell cycle arrest" associated with a particular secretome, could be at the root of a break in homeostasis and the development of the disease. We characterized senescent mesenchymal stem/stromal cells and showed that these cells lost their anti-senescent properties on chondrocytes in vitro and were able to drive the pathology in vivo.In a second step, we showed the implication of one of the proteins secreted by senescent mesenchymal stem/stromal cells, "Chitinase-like 3 protein 1" in the pathophysiology of osteoarthritis. Its expression level in synovial tissue is correlated with cartilage degradation and with senescence- and osteoarthritis- markers expression. In addition, Chi3L1 causes mesenchymal stem/stromal cells senescence which in turn are able to spread senescence syndroma to chondrocytes.Taken together, our results demonstrate the importance of cellular senescence and senescent-associated microenvironment in the pathophysiology of osteoarthritis. We also suggest that specific targeting of senescent mesenchymal stem/stromal cells could be an promising therapy to cure Osteoarthritis.