Consequences of irradiation on bone and marrow phenotypes, and its relation to disruption of hematopoietic precursors

Abstract

The rising levels of radiation exposure, specifically for medical treatments and accidental exposures, have added great concern for the long term risks of bone fractures. Both the bone marrow and bone architecture are devastated following radiation exposure. Even sub-lethal doses cause a deficit to the bone marrow microenvironment, including a decline in hematopoietic cells, and this deficit occurs in a dose dependent fashion. Certain cell phenotypes though are more susceptible to radiation damage, with mesenchymal stem cells being more resilient than the hematopoietic stem cells. The decline in total bone marrow hematopoietic cells is accompanied with elevated adipocytes into the marrow cavity, thereby inhibiting hematopoiesis and recovery of the bone marrow microenvironment. Poor bone marrow is also associated with a decline in bone architectural quality. Therefore, the ability to maintain the bone marrow microenvironment would hinder much of the trabecular bone loss caused by radiation exposure, ultimately decreasing some comorbidities in patients exposed to radiation.

Impacts of Terrestrial Ionizing Radiation on the Hematopoietic System

“…A stimulated response induced by exposure to low-dose radiation is also reported [108]. The immune-suppressive effects are reported from high doses of radiation, but it is also reported that long-term exposure to low-dose radiation can also alter immune response by the destruction of certain cell types [109].…”

“…A study found that bone marrow can be damaged from radiation exposure. The sub-lethal doses can cause a deficit to the bone marrow microenvironment, and thereby a decline in hematopoietic cells [109].…”

Inducible Models of Bone Loss

“…Irradiation is known to have a negative effect on the bone marrow microenvironment, leading to a reduction in bone mass post-irradiation (Green & Rubin 2014). This is a straightforward method for the induction of bone loss, but systemic radiation effects must also be considered when performing the experiment.…”

Parathyroid Hormone (1–34) Transiently Protects Against Radiation-Induced Bone Fragility

“…Focal radiation (5 × 4 Gy) has been shown both to decrease local osteoblast and osteoclast numbers, and to reduce marrow progenitor cell (MPC) self-renewal and osteoblastic differentiation capabilities in a mouse model [38]. In addition to depleting hematopoietic progenitor cell (HPC) populations, radiation may indirectly suppress HPC proliferation through increased marrow adiposity [37, 39, 40]. Radiation can also damage progenitor stem cell populations through direct destruction of bone vasculature, which is critical for maintenance of the stem cell niches [38].…”