Could suppression of Gαq/11 signaling be a promising target for treating bone loss?

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.

In a new study published in the journal 'Calcified Tissue International and Musculoskeletal Research', investigators used transgenic mice that specifically overexpress Gα₁₁ to compare in vivo the effects of intermittent PTH and treadmill exercise on bonearchitecture, strength and histology. They also investigated how osteoblastic elevation of Gα₁₁ (without constitutive Gα_q/11 activity) in these mice influences the skeletal response to anabolic bone therapies.

Professor Jane Mitchell, 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."