Removing Senescent Cells Stops Extra-Skeletal Bone Growth in Mice
Clearing senescent cells from the body may prove a treatment for yet another condition, one that is both rare and currently lacking in effective therapies. In this case it’s a genetic condition called fibrodysplasia ossificans progressiva or FOP. In those affected, even mild injury, such as an injection, can cause soft tissue swelling that leads muscle tissue to turn into bone. People with this disease can find themselves immobilized by loss of soft tissue by mid-life and rarely live past their 50s.
Senescent cells, sometimes called zombie cells, stop functioning properly but remain in the body, circulating and causing other cells to malfunction and produce symptoms of aging such as osteoporosis, frailty, loss of sight, and cancer. In this case, the researchers state in their paper in the Journal of Bone and Mineral Research that senescent cells along with unregulated cell signaling of activin-A are plausible mechanisms for episodic flare-ups of FOP. They analyzed biopsied lesions from patients who were later diagnosed with FOP and conducted studies on FOP in mouse models. They found:
- Muscle injury in the mice induced senescent cell accumulation.
- Senescent cells were found in FOP lesions in patients.
- Genes associated with senescence were identified in the mice early after injury and resulted in cellular reprogramming prompting bone growth.
- Removal or clearance of senescent cells in mice reduced those reprogramming factors, resulting in near prevention of extra-skeletal ossification.
The researchers concluded that senolytic drugs, discovered at Mayo Clinic, can be used to reduce the impact of FOP in the mouse model and therefore have therapeutic potential. Additional study, including research on the more common forms of non-hereditary extra-skeletal ossification (e.g., due to blunt trauma, burns, etc.) and clinical trials are needed to determine safety and effectiveness in patients.
The research is supported by the Radiant Hope Foundation, the Robert and Arlene Kogod Professorship in Geriatric Medicine, the International Fibrodysplasia Ossificans Progressiva Association, and at the University of Pennsylvania the Center for Research in FOP and Related Disorders, the Ian Cali Endowment for FOP Research, and the Isaac and Rose Nassau Professorship of Orthopaedic Molecular Medicine.
Authors on the paper from Mayo Clinic are Haitao Wang, Ph.D., Qiang Zhang, Ph.D. and Robert Pignolo, M.D., Ph.D. Frederick Kaplan, M.D., is affiliated with the University of Pennsylvania. The complete paper can be found at the journal.
- Bob Nellis, Feb. 10, 2022