The Effect of OSM on MC3T3-E1 Osteoblastic Cells in Simulated Microgravity with Radiation

Abstract

Bone deterioration is a challenge in long-term spaceflight with significant connections to patients experiencing disuse bone loss. Prolonged unloading and radiation exposure, defining characteristics of space travel, have both been associated with changes in inflammatory signaling via IL-6 class cytokines in bone. While there is also evidence for perturbed IL-6 class signaling in spaceflight, there has been scant examination of the connections between microgravity, radiation, and inflammatory stimuli in bone. Our lab and others have shown that the IL-6 class cytokine oncostatin M (OSM) is an important regulator of bone remodeling. We hypothesize that simulated microgravity alters osteoblast OSM signaling, contributing to the decoupling of osteolysis and osteogenesis in bone homeostasis. To test this hypothesis, we induced OSM signaling in murine MC3T3-E1 pre-osteoblast cells cultured in modeled microgravity using a rotating wall vessel bioreactor with and without exposure to radiation typical of a solar particle event. We measured effects on inflammatory signaling, osteoblast activity, and mineralization. Results indicated time dependent interactions among all conditions in the regulation of IL-6 production. Furthermore, OSM induced the transcription of OSM receptor ß, IL 6 receptor α subunits, collagen α1(I), osteocalcin, sclerostin, RANKL, and osteoprotegerin. Measurements of osteoid mineralization suggest that the spatial organization of the osteoblast environment is an important consideration in understanding bone formation. Taken together, these results support a role for altered OSM signaling in the mechanism of microgravity-induced bone loss.

HIGH expression of OSM and IL-6 are associated with decreased breast cancer survival: synergistic induction of IL-6 secretion by OSM and IL-1β

“…Our studies with breast cancer patients showed that high serum levels of OSM and IL-6 are correlated, and OSM has been shown to induce IL-6 expression in smooth muscle cells, osteoblasts, and astroglioma cells [49, 57, 58]. This prompted us to investigate whether OSM signals mammary tumor cells to increase IL-6 expression in vivo .…”

Simulated Microgravity and Low-Dose/Low-Dose-Rate Radiation Induces Oxidative Damage in the Mouse Brain

“…The question of whether low-dose radiation response is modulated by microgravity is an important aspect of risk assessment that has received little attention in the literature (32,33). The objective of the current study was to use a ground-based animal model for spaceflight, combining radiation and HLU simultaneously for 21 days, to assess FIG.…”

“…The reasons for this finding remain unclear. However, others have observed similarly divergent responses to radiation and simulated microgravity in osteoblast inflammatory signaling (32) and bystander signaling in plants (43). HLU in combination with LDR radiation may induce apoptotic protein expression and apoptosis with different timing compared to each stressor alone.…”

Simulated microgravity modulates the mesenchymal stromal cell response to inflammatory stimulation

“…OSM supplementation upregulated collagen α1(I) and osteocalcin genes but had no significant effect on sclerostin transcription. RCCS downregulated collagen α1(I) and osteocalcin while upregulating sclerostin 38 .…”