Therapy-Induced Senescence Drives Bone Loss
Abstract
Chemotherapy is important for cancer treatment, however, toxicities limit its use. While great strides have been made to ameliorate the acute toxicities induced by chemotherapy, long-term comorbidities including bone loss remain a significant problem. Chemotherapy-driven estrogen loss is postulated to drive bone loss, but significant data suggests the existence of an estrogen-independent mechanism of bone loss. Using clinically relevant mouse models, we showed that senescence and its senescence-associated secretory phenotype (SASP) contribute to chemotherapy-induced bone loss that can be rescued by depleting senescent cells. Chemotherapy-induced SASP could be limited by targeting the p38MAPK-MK2 pathway, which resulted in preservation of bone integrity in chemotherapy-treated mice. These results transform our understanding of chemotherapy-induced bone loss by identifying senescent cells as major drivers of bone loss and the p38MAPK–MK2 axis as a putative therapeutic target that can preserve bone and improve a cancer survivor's quality of life.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Mar 01, 2020
- Source ID
- 10.1158/0008-5472.can-19-2348
Entities
People
- Bhavna Murali
- Biancamaria Ricci
- Darren Baker
- Dinesh Thotala
- Douglas V Faget
- Jan M. Van Deursen
- Joseph Monahan
- Julie K Schwarz
- Qihao Ren
- Roberta Faccio
- Sheila A. Stewart
- Tom Cole
- Xianmin Luo
- Zhangting Yao
Organizations
- Congressionally Directed Medical Research Programs
- Glenn Foundation for Medical Research
- Mayo Clinic
- National Cancer Institute
- National Institute of General Medical Sciences
- National Institute on Aging
- Shriners Hospitals for Children
- United States Department of Health and Human Services
- Washington University School of Medicine
- Washington University in St. Louis