J.D. Wheat Veterinary Orthopedic Research Laboratory

Cell and Molecular Biology

Bone cells and their mechanical environment:

Mechanotransduction

Understanding the influence of the biophysical environment on normal cell biology has been our central focus for some time. Many of the mechanical stimuli osteoblasts respond to, and the downstream signaling events that are initiated have been identified. What is still unknown, however, is the identity of a cell-bound mechanosensor or mechanosensory complex, which would initiate the conversion of a localized biophysical signal into an intracellular signaling response. We are investigating the role of annexins, calcium-dependent phospholipid-binding proteins, as a possible mechanosensors. We are also looking at the role of lipid rafts in mechanosignaling since annexins can localize to these membrane regions, which may be the initiation points of mechanosensing.

Photo: Cell and Molecular Biology image

Publications

Yellowley, C.E., Jacobs, C.R., Zhou, Z., Li, Z. and Donahue, H.J. (1997) Effects of fluid flow on intracellular calcium in bovine articular chondrocytes. Am. J. Physiol. 273:42 ppC30-C36.

Jacobs, C.R., Yellowley, C.E., Davis, B.R, Zhou, Z. and Donahue, H.J. (1998) Differential effect of steady versus oscillating flow on bone cells. Journal of Biomechanics. 31; 969-976 Winner of the 1998 Research Award of the European Society of Biomechanics

Yellowley, C.E., Jacobs, C.R and Donahue, H.J. (1999) Mechanisms contributing to fluid-flow-induced Ca2+ mobilization in articular chondrocytes. Journal of Cellular Physiology 180:402-408.

You, J., Yellowley, C.E., Donahue, H.J., Zhang, Y., Chen, Q. and Jacobs, C.R. (2000) Substrate deformation levels associated with routine physical activity are less stimulatory to bone cells relative to loading-induced oscillatory fluid flow. Journal of Biomechanical Engineering. August Volume122, Issue 4 pp. 387-393.

Edlich M, Yellowley, C.E., Jacobs, C.R and Donahue, H.J. (2001) Oscillating fluid flow regulates cytosolic calcium concentration in bovine articular chondrocytes.  Journal of Biomechanics Vol. 34 p 59-65.

You, J., Reilly, G.R., Zhen, X., Yellowley, C.E., Chen, Q., Donahue, H.J., and Jacobs, C.R. (2001) Osteopontin gene regulation by oscillatory fluid flow via intracellular calcium mobilization and activation of mitogen-activated protein kinase in MC3T3-E1 osteoblasts. Journal of Biological Chemistry 276: 13365-13371.

Sharma, R., Yellowley, C.E., Civelek, M., Ainslie, K., Hodgson, L., Tarbell, J. M. and Donahue, H.J. (2002) Intracellular calcium changes in rat aortic smooth muscle cells in response to fluid flow. Annals of Biomedical Engineering Mar;30(3):371-8.

Yellowley, C.E., Hancox, J.C. and Donahue, H.J. (2002) Effects of cell swelling on intracellular calcium and membrane currents in bovine articular chondrocytes. J Cell Biochem. 86(2):290-301.

Saunders, M.M., You, J., Zhou, Z., Li, Z., Yellowley, C.E., Kunze, E., Jacobs, C.R. and Donahue, H.J. (2003) Fluid flow-induced Prostaglandin E2 response of osteoblastic ROS 17/2.8 cells is gap junction-mediated and independent of cytosolic calcium. Bone Apr;32(4):350-6.

Haut Donahue, T.L., Haut, T.R., Yellowley, C.E., Donahue, H.J. and Jacobs, C.R. (2003). Mechanosensitivity of bone cells to oscillating fluid flow induced shear stress may be modulated be chemotransport. Journal of Biomechanics 36 (9) 1363-1371.

Reilly, G.C., Haut, T.R., Yellowley, C.E., Donahue, H.J. and Jacobs, C.R. (2003) Fluid flow induced PGE2 release by bone cells is reduced by glycocalyx degradation whereas calcium signals are not. Biorheology; Volume 40, No.6 p591-603.

Alford, A.I., Yellowley, C.E., Jacobs, C.R., and Donahue, H.J. (2003) Increases in cytosolic calcium, but not fluid flow, affect aggrecan mRNA levels in articular chondrocytes. Journal of Cellular Biochemistry 90: 938-944.

Haut Donahue, TL., Genetos, D.c., Donahue, H.J., Jacobs, C.R. and Yellowley, C.E. (2004). Annexin V disruption impairs mechanically-induced calcium signaling in osteoblast cells. Bone 35: 656-663.

Li, Y., Batra, N.N., You, L., Meier, S.C., Yellowley, C.E., Jacobs, C.R. (2004) Oscillatory fluid flow affects human marrow stromal cell proliferation and differentiation. Journal of Orthopedic Research Nov; 22(6):1283-9.

Edlich, M., Yellowley, C.E., Jacobs, C.R. and Donahue, H.J. (2004) Cycle number and waveform of fluid flow affect bovine articular chondrocytes. Biorheology 41 (3-4) 315-322.

Batra, NN., Li, Y., Yellowley, C.E., You, L., Malone, AM., Kim, CH. and Jacobs, C.R. (2005) Effects of short-term recovery periods on fluid-induced signaling in osteoblastic cells. J. Biomech. Sep;38(9):1909-17.

Kim, C., Yellowley, C.E. and Jacobs, C.R. (2006) Oscillatory fluid flow induced shear stress decreases osteoclastogenic activity through regulation of RANKL and OPG. Bone. Nov; 39(5):1043-1047.

Genetos, D.C., Kephart, C.J., Zhang, Y., Yellowley, C.E. and Donahue, H.J. (2007) Oscillatory fluid flow activation of gap junction hemichannels promotes ATP release in MLO-Y4 osteocytes. Journal of Cellular Physiology. July;212(1):207-14