Suppress GAQ/11 Signaling, Curb Bone Loss?

Is it possible that inhibiting signaling of the protein Gα₁₁ can contribute to halting bone loss? Maybe, say researchers from the University of Toronto.

As indicated in the August 9, 2016 news release, “Intermittent parathyroid hormone treatment (iPTH) and mechanical loading through exercise have both been shown to stimulate bone formation. These osteoanabolic stimuli are partially mediated by G protein-coupled receptors. Previous studies have suggested that enhanced signalling through the Gα_q/11 pathway inhibits the bone-building actions of PTH, however the influence of enhanced Gα_q/11 pathway on exercise has not been reported in vivo.”

Professor Jane Mitchell, Ph.D., associate chair, Department of Pharmacology and Toxicology. University of Toronto, stated, “In summary, our studies demonstrate that elevated Gα₁₁ in osteoblast lineage cells inhibits the osteoanabolic effects of intermittent PTH and inclined treadmill exercise. That Gα₁₁ mediates these functions in the bone microenvironment may indicate that inhibition of Gα₁₁ signaling can augment the responses to PTH and exercise in increasing bone mass and strength, and may be a suitable candidate to target for treating bone loss.”

Asked to define G protein-coupled receptors, Dr. Mitchell told OTW, “These are a large family of receptor proteins expressed on the surface of all cells. They are activated by binding hormones, neurotransmitters and other signals coming to the cell. When activated, these receptors couple to G proteins on the inside of the cell membrane and these G proteins regulate systems inside of the cell that change cellular activity.”

“Bone mineral density and strength is controlled by an array of hormonal, genetic, nutritional and environmental factors. Our work has shown that when we increase the expression of the G₁₁ protein in osteoblasts, the cells that make bone, mice no longer increased bone in response to exercise or parathyroid hormone therapy. This may mean that normal variation in G protein expression is also a factor determining response to bone-building stimuli. We are currently testing how the mice with different levels of G protein expression heal bone after fracture.”