Lecture by Ita Bab on April 5

Itai Bab, Bone Laboratory, The Hebrew University of Jerusalem, Jerusalem 91120, Israel will present:
"Central IL-1 Signaling Regulates Bone Mass Via the Parasympathetic Nervous System."

Monday April 5, 2010
11:00 a.m.
Gill Conference Room

Abstract: We have previously observed that central IL-1 stimulates bone mass accrual by favoring bone formation over bone resorption. This activity appears to oppose the adrenergic skeletal tone, which restrains bone formation and enhances bone resorption. Hence, we hypothesized that the central IL-1 signals are communicated to the skeleton by the parasympathetic nervous system (PSNS). Indeed, we show now the presence of nicotinic, but not muscarinic acetylcholine receptors (nAChRs) in osteoblasts and osteoclasts. nAChR agonists stimulate osteoblast number. The same agonists inhibit bone resorption by inducing premature osteoclastogenesis and osteoclast apoptosis. Additional cholinergic components present in the skeleton are acetylcholine (ACh) as well as parasympathetic nerve fibers immunohistochemically positive for acetyltransferase and the vesicular ACh transporter. The membrane bound and soluble ACh esterases (AChEs), the ACh degrading enzymes, are also present in bone cells. Following inoculation of a recombinant pseudorabies virus at the distal femoral metaphysis, cells containing the immunoreactive virus were identified in the sacral part of intermediolateral cell column, which consists of parasympathetic neurons. Taken together, these data establish the occurrence of skeletal parasympathetic innervation. PSNS activation by administering the peripheral AChE inhibitor pyridostigmine (PS) to mice during bone mass accrual leads to a marked stimulation of bone mass and ACh content. Mice with silenced central IL-1 signaling show low bone mass and ACh content, which cannot be rescued by PS. These findings demonstrate that during bone mass accrual central IL-1 signaling maintains a positive bone remodeling balance by controlling a skeletal parasympathetic tone.

Announced by:
Heather Bradshaw, Ph.D.
Assistant Professor
Psychological and Brain Sciences
Indiana University
1101 East 10th Street
Bloomington, IN 47405
hbbradsh@indiana.edu
812-856-1559 (office)
812-855-0652 (lab)