CNPY2 modulates senescence-associated secretory phenotype in tendon stem/progenitor cells.

Abstract

Age-related diseases are often linked to chronic inflammation. Senescent cells secrete inflammatory cytokines, chemokines and matrix metalloproteinases, collectively referred to as the senescence-associated secretory phenotype (SASP). The current study discovered that aging leads to the accumulation of senescent tendon stem/progenitor cells (TSPCs) in tendon tissue, resulting in the development of a SASP. Conditioned medium from aged TSPCs induced cellular inflammation in young TSPCs. In addition, we found that Canopy homolog 2 (CNPY2) expression is reduced during tendon aging. CNPY2 deficiency causes TSPCs senescence and SASP. Our findings showed that the NF-κB signaling pathway is activated in CNPY2 knockdown TSPCs, pharmacological inhibition of NF-κB signaling pathway with BMS-345541 attenuated SASP of senescent TSPCs, which indicated that CNPY2 regulates TSPCs SASP might through NF-κB signaling pathway. Our findings suggested that CNPY2 plays an important role in TSPCs senescence and SASP, CNPY2 could be a promising target for age-related tendon disorders.