TY - JOUR
T1 - Senescent cells and osteoarthritis
T2 - A painful connection
AU - Jeon, Ok Hee
AU - David, Nathaniel
AU - Campisi, Judith
AU - Elisseeff, Jennifer H.
N1 - Funding Information:
The authors gratefully acknowledge financial support from Unity Biotechnology, the Morton Goldberg Chair, the Bloomberg~ Kimmel Institute for Cancer Immunotherapy, the NIH (AG009909), and the Office of the Assistant Secretary of Defense for Health Affairs through the Peer Reviewed Medical Research Program (W81XWH-17-1-0627).
Publisher Copyright:
© 2018 American Society for Clinical Investigation. All rights reserved.
PY - 2018/4/2
Y1 - 2018/4/2
N2 - Senescent cells (SnCs) are associated with age-related pathologies. Osteoarthritis is a chronic disease characterized by pain, loss of cartilage, and joint inflammation, and its incidence increases with age. For years, the presence of SnCs in cartilage isolated from patients undergoing total knee artificial implants has been noted, but these cells' relevance to disease was unclear. In this Review, we summarize current knowledge of SnCs in the multiple tissues that constitute the articular joint. New evidence for the causative role of SnCs in the development of posttraumatic and age-related arthritis is reviewed along with the therapeutic benefit of SnC clearance. As part of their senescence-associated secretory phenotype, SnCs secrete cytokines that impact the immune system and its response to joint tissue trauma. We present concepts of the immune response to tissue trauma as well as the interactions with SnCs and the local tissue environment. Finally, we discuss therapeutic implications of targeting SnCs in treating osteoarthritis.
AB - Senescent cells (SnCs) are associated with age-related pathologies. Osteoarthritis is a chronic disease characterized by pain, loss of cartilage, and joint inflammation, and its incidence increases with age. For years, the presence of SnCs in cartilage isolated from patients undergoing total knee artificial implants has been noted, but these cells' relevance to disease was unclear. In this Review, we summarize current knowledge of SnCs in the multiple tissues that constitute the articular joint. New evidence for the causative role of SnCs in the development of posttraumatic and age-related arthritis is reviewed along with the therapeutic benefit of SnC clearance. As part of their senescence-associated secretory phenotype, SnCs secrete cytokines that impact the immune system and its response to joint tissue trauma. We present concepts of the immune response to tissue trauma as well as the interactions with SnCs and the local tissue environment. Finally, we discuss therapeutic implications of targeting SnCs in treating osteoarthritis.
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U2 - 10.1172/JCI95147
DO - 10.1172/JCI95147
M3 - Review article
C2 - 29608139
AN - SCOPUS:85045033986
SN - 0021-9738
VL - 128
SP - 1229
EP - 1237
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
IS - 4
ER -