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MEMBRANE TRANSPORTERS, ION CHANNELS, AND PUMPS

Importance of melastatin-like transient receptor potential 7 and magnesium in the stimulation of osteoblast proliferation and migration by platelet-derived growth factor

Laboratoire du métabolisme osseux, Centre BioMed, Département des Sciences Biologiques, Université du Québec à Montréal, Montreal, Quebec, Canada

Submitted 27 November 2008 ; accepted in final form 21 May 2009

Bone is a dynamic tissue that is continuously being remodeled throughout life. Specialized cells called osteoclasts transiently break down old bone (resorption process) at multiple sites as other cells known as osteoblasts are replacing it with new tissue (bone formation). Usually, both resorption and formation processes are in balance and thereby maintain skeletal strength and integrity. This equilibrium is assured by the coordination of proliferation, migration, differentiation, and secretory functions of the osteoblasts, which are essential for adequate formation and resorption processes. Disturbances of this equilibrium may lead to decreased bone mass (osteoporosis), increased bone fragility, and susceptibility to fractures. Epidemiological studies have linked insufficient dietary magnesium (Mg²⁺) intake in humans with low bone mass and osteoporosis. Here, we investigated the roles of Mg²⁺ and melastatin-like transient receptor potential 7 (TRPM7), known as Mg²⁺ channels, in human osteoblast cell proliferation and migration induced by platelet-derived growth factor (PDGF), which has been involved in the bone remodeling process. PDGF promoted an influx of Mg²⁺, enhanced cell migration, and stimulated the gene expression of TRPM7 channels in human osteoblast MG-63 cells. The stimulation of osteoblast proliferation and migration by PDGF was significantly reduced under culture conditions of low extracellular Mg²⁺ concentrations. Silencing TRPM7 expression in osteoblasts by specific small interfering RNA prevented the induction by PDGF of Mg²⁺ influx, proliferation, and migration. Our results indicate that extracellular Mg²⁺ and TRPM7 are important for PDGF-induced proliferation and migration of human osteoblasts. Thus Mg²⁺ deficiency, a common condition among the general population, may be associated with altered osteoblast functions leading to inadequate bone formation and the development of osteoporosis.

TRPM7 channels; osteoblasts; adhesion