Parathyroid hormone protects osteocytes from radiation-induced cell death and DNA damage
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Citation
Abstract
Bone is a dynamic, living tissue that constantly undergoes remodeling through the coordinated actions of osteoblasts (cells that build bone) and osteoclasts (cells that break down bone). Parathyroid hormone (PTH) is used clinically to treat osteoporosis due to its anabolic actions on bone. PTH binds to its receptor (PPR), which is highly expressed in cells of the osteoblastic lineage, including osteocytes. Radiotherapy, a common cancer treatment, adversely impacts bone health by impairing osteoblast and osteoclast functions, leading to conditions such as osteopenia and osteoporosis. Pre-clinical and cell culture studies have indicated that radiotherapy damages bone. This study investigates whether pretreatment with parathyroid hormone (PTH1-34) can protect osteocytes from radiation-induced DNA damage and cell death. We utilized a conditionally immortalized murine osteocytic cell line, Ocy454-12H, treated it with PTH, and exposed it to varying radiation doses. Results showed that PTH significantly reduced γH2AX foci, indicating decreased DNA damage. qPCR analysis revealed modulated expression of DNA damage-related genes (FOXO1, P53, MKi67), suggesting enhanced DNA repair and reduced apoptosis. Additionally, PTH mitigated radiation-induced bystander effects, reducing osteoclast activity. These findings highlight PTH's potential as a therapeutic agent to protect bone health in radiotherapy patients.