Simulated microgravity suppresses osteoblast phenotype, Runx2 levels and AP-1 transactivation.
Conditions of disuse such as bed rest, space flight, and immobilization result in decreased mechanical loading of bone, which is associated with reduced bone mineral density and increased fracture risk. Mechanisms involved in this process are not well understood but involve the suppression of osteoblast function. To elucidate the influence of mechanical unloading on osteoblasts, a rotating wall vessel (RWV) was employed as a ground based model of simulated microgravity. Mouse MC3T3-E1 osteoblasts were grown on microcarrier beads for 14 days and then placed in the RWV for 24 h. Consistent with decreased bone formation during actual spaceflight conditions, alkaline phosphatase and osteocalcin expression were decreased by 80 and 50%, respectively. In addition, runx2 expression and AP-1 transactivation, key regulators of osteoblast differentiation and bone formation, were reduced by more than 60%. This finding suggests that simulated microgravity could promote dedifferentiation and/or transdifferentiation to alternative cell types; however, markers of adipocyte, chondrocyte, and myocyte lineages were not induced by RWV exposure. Taken together, our results indicate that simulated microgravity may suppress osteoblast differentiation through decreased runx2 and AP-1 activities.
Ontiveros
C
C
Department of Physiology, Michigan State University, 2201 Biomedical Physical Science Bldg., East Lansing 48824, USA.
McCabe
Laura R
LR
D016475:3T3 Cells; D000469:Alkaline Phosphatase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D018929:Cell Culture Techniques / Q000379:methods; D050659:Core Binding Factor Alpha 1 Subunit; D006801:Humans; D051379:Mice; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D010006:Osteoblasts / Q000166:cytology / Q000502:physiology*; D015675:Osteocalcin / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D013026:Space Flight; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation / Q000502:physiology*; D018474:Weightlessness Simulation
D050659:Core Binding Factor Alpha 1 Subunit; D009363:Neoplasm Proteins; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D015675:Osteocalcin; D000469:Alkaline Phosphatase