Correlation Engine 2.0
Clear Search sequence regions

  • abt263 (8)
  • apoptosis (1)
  • articular cartilage (2)
  • bone (1)
  • cartilage (4)
  • cellular (1)
  • cytokines (1)
  • DMM (1)
  • humans (1)
  • navitoclax (3)
  • rat (4)
  • senescent cells (6)
  • synovium (1)
  • Sizes of these terms reflect their relevance to your search.

    Cell senescence is a chronic process associated with age-related degenerative diseases such as osteoarthritis (OA). Senescent cells (SnCs) accumulate in the articular cartilage and synovium, leading to OA pathologies. The accumulation of SnCs in the cartilage results in a senescence-associated secretory phenotype (SASP) and age-related inflammation and dysfunction. Selective removal of SnCs by senolytic agent as a therapeutic strategy has been developed recently. In this study, we examined the ability of the senolytic drug ABT263 (navitoclax) to clear SnCs and further evaluated the therapeutic effect of ABT263 on post-traumatic OA. Monolayer and 3D pellet cultured osteoarthritic chondrocytes were used to evaluate the effect of ABT263 in vitro and a DMM rat model was established for in vivo experiments. We found that ABT263 reduced the expression of inflammatory cytokines and promoted cartilage matrix aggregation in OA chondrocyte pellet culture by inducing SnC apoptosis. Moreover, OA pathological changes in the cartilage and subchondral bone in post-traumatic OA rat were alleviated by ABT263 intra-articular injection. These results demonstrated that ABT263 not only improves inflammatory microenvironment but also promotes cartilage phenotype maintenance in vitro. Furthermore, ABT263 might play a protective role against post-traumatic OA development. Therefore, strategies targeting SnC elimination might be promising for the clinical therapy of OA.


    Hao Yang, Cheng Chen, Hao Chen, Xiaojun Duan, Juan Li, Yi Zhou, Weinan Zeng, Liu Yang. Navitoclax (ABT263) reduces inflammation and promotes chondrogenic phenotype by clearing senescent osteoarthritic chondrocytes in osteoarthritis. Aging. 2020 Jul 01;12(13):12750-12770

    Expand section icon Mesh Tags

    Expand section icon Substances

    PMID: 32611834

    View Full Text