Date of Award
Master of Science
Osteoblasts form bone and regulate the activity of other bone cells. Lysophosphatidic acid (LPA) is a lipid mediator that, in other systems, stimulates cell proliferation, survival and migration. We investigated LPA signaling and function in osteoblasts. Transcripts encoding multiple LPA receptors were identified. LPA induced transient elevation of cytosolic calcium ([Ca ];) in primary osteoblasts and UMR-106 osteoblast-like cells, effects that were attenuated by pertussis toxin, implicating Gj. Moreover, [Ca2+]j elevation was found to arise by release from intracellular stores. An LPAi receptor antagonist blocked bone formation in cultures of primary osteoblasts. Finally, LPA induced membrane blebbing in MC3T3-E1 osteoblast-like cells - a process that was sensitive to inhibition of Rho-associated protein kinase or chelation of cytosolic calcium. Thus, LPA activates calcium-mobilizing receptors in osteoblastic cells to induce morphological changes. As well, LPA promotes bone formation in vitro. In vivo, LPA may regulate osteogenesis in an autocrine or paracrine manner.
Bridge, Karen Ann, "LYSOPHOSPHATIDIC ACID RECEPTOR SIGNALING AND FUNCTION IN OSTEOBLASTS" (2011). Digitized Theses. 3429.