Jacobs:Research:Mechanotransduction in Bone via Oscillatory Fluid Flow in vitro

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Osteocytes sense fluid flow via the primary cilium

  • Our group has identified the primary cilium as a critical mechanosensing organelle in osteocytes. Impairing primary cilia formation abrogates how cells sense fluid flow mechanical stimulation. This flow sensing is mediated by stores of proteins that localize to primary cilia including adenylyl cyclases, and the ion channels TRPV4 and PC2.
  • Milos Spasic is developing pharmacologic and gene-based strategies to modulate primary cilia-mediated mechanosensing to enhance osteogenesis.
  • Emily Moore's work utilizes site-directed mutagenesis and DNA manipulation strategies to further our understanding of how calcium regulates some of the proteins critical to cell mechanosensing.
  • Michael Duffy is uncovering novel proteins which may regulate primary cilia-mediated mechanosensing.

Intercellular fluid flow

  • Our previous work has demonstrated that mechanically stimulated osteocytes secrete soluble paracrine signals to direct stem cell osteogenic differentiation. Milos Spasic is now continuing this work to examine paracrine signaling to bone forming osteoblasts, and how pharmacologically manipulating osteocyte mechanosensing can augment osteogenic signaling.