Non-neuronal cholinergic stimulation favors bone mass accrual

Faleh Tamimi^1*Hazem Eimar²Sharifa Alebrahim²Garthiga Manickam²Ahmed Ebraheem Al Subaie²Lina Abu-Nada^3*Iskandar Tamimi²Monzur Murshed^2*

• ¹Qatar University, Doha, Qatar
• ²McGill University, Montreal, Canada
• ³University of Sharjah, Sharjah, United Arab Emirates

Non-neuronal cholinergic receptors are expressed in immune cells and their stimulation has been shown to regulate the secretion of several cytokines. Some of these cytokines, such as interleukin-17 (IL-17), IL-23, interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α), are known to regulate bone mass. Accordingly, we hypothesize that stimulating cholinergic receptors in non-neuronal cells, such as immune cells, promotes bone mass accrual. To test this hypothesis, we used neostigmine, a drug that increases acetylcholine levels by inhibiting acetylcholinesterases in the peripheral tissues. Here, we show that 6 weeks of neostigmine treatment promotes bone mass accrual in endochondral bones of both the axial and appendicular skeleton in mice. Moreover, the administration of neostigmine for 2 weeks accelerated the healing process of the surgically induced bone defects in rats. The body mass index, body weight, visceral fat pad weight and epinephrine levels in the neostigmine-treated mice were similar to those of saline-treated mice, indicating that neostigmine favored bone mass accrual by acting peripherally rather than centrally.