Differences in responses to X-ray exposure between osteoclast and osteoblast cells

Abstract

Radiation-induced bone loss is a potential health concern for cancer patients undergoing radiotherapy. Enhanced bone resorption by osteoclasts and decreased bone formation by osteoblasts were thought to be the main reasons. In this study, we showed that both pre-differentiating and differentiating osteoclasts were relatively sensitive to X-rays compared with osteoblasts. X-rays decreased cell viability to a greater degree in RAW264.7 cells and in differentiating cells than than in osteoblastic MC3T3-E1 cells. X-rays at up to 8 Gy had little effects on osteoblast mineralization. In contrast, X-rays at 1 Gy induced enhanced osteoclastogenesis by enhanced cell fusion, but had no effects on bone resorption. A higher dose of X-rays at 8 Gy, however, had an inhibitory effect on bone resorption. In addition, actin ring formation was disrupted by 8 Gy of X-rays and reorganized into clusters. An increased activity of Caspase 3 was found after X-ray exposure. Actin disorganization and increased apoptosis may be the potential effects of X-rays at high doses, by inhibiting osteoclast differentiation. Taken together, our data indicate high radiosensitivity of osteoclasts. X-ray irradiation at relatively low doses can activate osteoclastogenesis, but not osteogenic differentiation. The radiosensitive osteoclasts are the potentially responsive cells for X-ray-induced bone loss.

Combined Effects of Simulated Microgravity and Radiation Exposure on Osteoclast Cell Fusion

“…In this study, we investigated the formation of multinucleated osteoclast cells after γ irradiation at a range of doses between 0.1 and 1 Gy in RAW 264.7 cells. Analysis of survival of the cells indicated a typical dose response, consistent with the reported study showing that these cells are radiosensitive [ 35 ]. The cell concentration after 1 Gy γ irradiation was about 60% of the non-irradiated samples after a 5-day culture.…”

The Influence of Radiation on Bone and Bone Cells—Differential Effects on Osteoclasts and Osteoblasts

“…In addition, X-rays, applied as a whole body irradiation of 2 Gy in mice, lead to an increase in osteoclastic differentiation and bone resorption, which is determined by increasing OC numbers and surface area, as well as increasing serum markers of bone resorption [ 58 ]. The differential effects of IR on OCs may depend on the applied dose of IR, as Zhang et al found that low doses of X-rays promoted osteoclastogenesis, whereas high doses led to the reduced differentiation of OCs, probably by the induction of apoptosis and actin disorganization [ 26 ]. As high doses of IR induce a damage response and inflammatory processes in affected tissues such as bone, the secretion of pro-inflammatory cytokines, e.g., tumor necrosis factor (TNF) α, interleukin (IL) -6 and IL-1 may be stimulated.…”

“…As all other tissues and cells, bone and the associated bone remodeling cells are also prone to radiation-induced damage. The effects of radiation on bone-associated cell types are especially important in questions of the medical application of IR, as well as for questions on environmental radiation effects [ 19 , 20 , 26 ].…”

Evaluation of longitudinal time-lapsedin vivomicro-CT for monitoring fracture healing in mouse femur defect models

“…As radiation effects are known to vary for different bone cell types and locations 30,34,35 , we assessed the four sub-volumes separately (Table 2). The applied micro-CT protocol did not significantly affect bone formation and resorption activities in the callus VOIs (DC, DP and FP) from week 5-6 with similar bone volume observed in week 5 and 6 for controls and scanned animals.…”

“…So far only few studies have focused on the underlying mechanisms of radiation-induced effects on bone mainly focusing on changes in expression profiles of osteoblast and osteoclast differentiation markers 30,35 . Recently, three consecutive in vivo studies by Chandra et al 36,53,54 showed, that radiation‐induced bone loss 53,54 is mediated via Sclerostin inhibition of osteoanabolic Wnt-signaling 36 .…”