The Effects of Dexamethasone and BMP-2 Delivered at Specific Time Points on Bone Regeneration

Presenter

Sophia Michelle Millan

Campus

UMass Amherst

Sponsor

Cathal J. Kearney, Department of Biomedical Engineering, UMass Amherst

Schedule

Session 2, 11:30 AM - 12:15 PM [Schedule by Time][Poster Grid for Time/Location]

Location

Poster Board A63, Campus Center Auditorium, Row 4 (A61-A80) [Poster Location Map]

Abstract

Dysregulated circadian rhythms have been linked to multiple diseases such as large bone loss due to impaired osteogenesis. Circadian rhythms are a 24-hour cycle, responsible for coordinating physiological and behavioral processes that can be entrained by stimuli such as temperature, glucocorticoids, light and sleep-wake cycles. In vitro, we can synchronize circadian rhythms in cell cultures by using temperature, or glucocorticoids. Here, MC3T3 pre-osteoblasts cells were used to investigate bone regeneration in in vitro assays. Previous studies using this cell line have shown glucocorticoids at low doses can reset circadian rhythms, and that bone morphogenetic proteins have a positive effect on bone formation. Dexamethasone, (a glucocorticoid) plays an important role during osteoblastic differentiation. Bone morphogenetic protein-2 (BMP-2) is a growth factor that promotes osteoblast maturation. Here, dexamethasone and BMP-2 were carefully delivered on a circadian schedule to synchronize rhythms and examine the role of circadian delivery on bone formation. Introducing circadian synchronization enhanced cell migration over non-synchronized controls as demonstrated by scratch assays. Dexamethasone treated cells closed the wound almost 20% more than the unsynchronized controls. Ongoing experiments measuring bone forming potential suggest there is an increase in alkaline phosphatase expression following dexamethasone and BMP-2 treatments, but further work is required to confirm this finding. Our next steps are to investigate how a 3D bone formation assay will respond to the techniques used in vitro. Ultimately, we believe that this work will unveil the role of circadian rhythms in bone regeneration.

Keywords

Tissue Engineering, Circadian Rhythms , Bone Regeneration, Dexamethasone, Osteoblasts

Research Area

Engineering

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