Publication Date

8-2014

Date of Final Oral Examination (Defense)

6-13-2014

Type of Culminating Activity

Thesis

Degree Title

Master of Science in Biology

Department

Biology

Supervisory Committee Chair

Cheryl Jorcyk, Ph.D.

Supervisory Committee Member

Julia Thom Oxford, Ph.D.

Supervisory Committee Member

Kristen A. Mitchell, Ph.D.

Abstract

Bone deterioration is a challenge in long-term spaceflight with significant connections to terrestrial 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 some evidence for perturbed IL-6 class signaling in spaceflight, there has been scant examination of the connections between free fall, 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 spaceflight alters osteoblast OSM signaling, contributing to the decoupling of osteolysis and osteogenesis. To test this hypothesis, we induced OSM signaling in murine MC3T3 E1 pre-osteoblast cells cultured in modeled free fall, using a rotating wall vessel bioreactor, and with exposure to radiation typical of a solar particle event. We measured effects on inflammatory signaling, osteoblast maturation and activity, osteoclast recruitment, and mineralization. There were time dependent interactions among all conditions in the regulation of IL-6 production. OSM induced transcription of the OSM receptor β and 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 spaceflight bone loss.

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