| Bone is an exquisitely mechanosensitive organ, and its homeostasis depends on the ability of bone cells to sense and respond to mechanical stimuli. One such stimulus is dynamic fluid flow, which triggers biochemical and transcriptional changes in bone cells by an unknown mechanism. The purpose of this dissertation is to expand the knowledge of how bone cells transduce mechanical stimuli into osteogenic responses. This dissertation covers one review of the literature and three studies. The review examines biomechanical regulation of bone marrow stromal cells and the role biomechanical regulation plays in lineage specific differentiation. The first study demonstrates that when marrow stromal cells, the precursors to the bone forming osteoblasts, are exposed to oscillatory fluid flow they release calcium ions from endoplasmic reticulum stores, and this calcium flux is necessary for flow induced osteogenic gene expression. The second study examines actin cytoskeletal changes with exposure to different fluid flow profiles and then determines that an intact actin cytoskeleton is not necessary for flow induced calcium flux or prostaglandin E2 release. The final study explores the role of primary cilia as mechanotransducers in bone cells. The study shows that bone cells possess primary cilia and that these primary cilia are required for osteogenic and bone resorptive responses to dynamic fluid flow. We also show that, unlike in kidney cells, primary cilia translate fluid flow into cellular responses in bone cells independently of calcium flux and stretch-activated ion channels. Understanding the mechanisms for mechanotransduction in bone could lead to therapeutic approaches to combat bone loss due to osteoporosis and disuse.*; *This dissertation is a compound document (contains both a paper copy and a CD as part of the dissertation). The CD requires the following system requirements: Windows MediaPlayer or RealPlayer. |
