Chemical sympathectomy‐induced changes in TH‐, VIP‐, and CGRP‐immunoreactive fibers in the rat mandible periosteum: Influence on bone resorption

Abstract

The expression of neurotransmitter receptors by bone cells supports the concept that the nervous system is a regulator of bone metabolism. The discrimination of the respective roles of the sensory and sympathetic nervous systems requires evidence of topographic relationships between the corresponding fibers and the cells involved in bone turnover, in vivo. In this study, the influence of the sympathetic system on bone resorption was assessed by using a synchronized model of cortical resorption along the mandible. The sympathetic system was destroyed by daily injections of guanethidine (40 mg/kg) for 25 days; a resorption wave was induced on day 21. The distribution of periosteal tyrosine-hydroxylase (TH)-, vasoactive intestinal polypeptide (VIP)-, and calcitonin gene-related peptide (CGRP)-immunoreactive (IR) fibers was studied by compartmentalizing the periosteum. Most fibers were located in the distal, non-osteogenic compartment. TH-IR fibers were located perivascularly, VIP-IR fibers were gathered at the boundary with the osteogenic compartment, and CGRP-IR fibers were scattered. Sympathectomy decreased the number of TH- and VIP-IR fibers and increased the number of CGRP-IR fibers, without changing their topography. After the injection of Fast blue, a retrograde fluorescent marker, over the periosteum, fluorescent neuronal cell bodies were found in the superior cervical ganglion (SCG). Many neurons were TH-IR and very few were VIP-IR. Sympathectomy decreased the numbers of fluorescent and TH-IR cell bodies. It also decreased the number of preosteoclasts and osteoclasts, which had a drastic effect on the cortical bone surface, as assessed by scanning electron microscopy. These data indicate that VIP-IR fibers have a strategic position close to the most peripheral and less differentiated, osteogenic cells, pointing to a functional relationship. As poorly differentiated osteogenic cells support preosteoclast differentiation, VIP-IR fibers may be involved in this process, as suggested by the smaller number of preosteoclasts in sympathectomized rats. Although VIP is predominantly a parasympathetic mediator, it seemed to be conveyed by sympathetic fibers, as shown by the marked effect of guanethidine treatment. Nevertheless, these fibers did not originate from the SCG, contrary to TH-IR fibers.

Spinal cord injury causes rapid osteoclastic resorption and growth plate abnormalities in growing rats (SCI-induced bone loss in growing rats)

“…Moreover, nerve fiber distribution has been shown to change in response to neurological injury. Induced sensory and sympathetic denervation dramatically alters the distribution of immunoreactive fibers within rat bone [21,46]. Neurological injury may result in physiological changes within the bone microenvironment, including shunt formation in blood circulation and changes in cytokine or neuro-osteotrophic factor expression, that ultimately lead to osteoclast activation and osteoblast inhibition.…”

“…Bone is densely innervated, and the observation of direct contact of nerve fibers and bone cells strongly supports a role of innervation in bone cell functions. A number of neuromediators have also been detected by immunocytochemistry in nerve fibers in bone [18][19][20][21][22][23]. These studies suggest an important role of the neural system in regulating bone cell functions, and ultimately in influencing bone homeostasis.…”

Histamine Promotes Osteoclastogenesis through the Differential Expression of Histamine Receptors on Osteoclasts and Osteoblasts

“…The recruitment of the monocytes reaches a maximum level 12 hours after induction and is complete 24 hours after induction; osteoclastic resorption follows the recruitment of the monocyte and peaks 4 days after induction. 7,18 Rats were locally treated by injecting histamine (4 l of a solution at 10 g/ml), mast cell degranulating agent c48/80 (4 l of a solution at 100 g/ml) or saline (vehicle, VEH) close to the site of resorption 19 8 hours after activation. Other rats were treated systemically with intramuscular injection of saline H1R antagonist mepyramine solution (1.5 mg/kg/day), saline H2R antagonist famotidine solution (10 mg/kg/day) or VEH, either beginning immediately after extractions (early treatment) or 24 hours later, ie, after inflammatory cell recruitment (delayed treatment).…”

Sympathectomy alters bone architecture in adult growing rats

“…Likewise, chemical sympathectomy of neonatal rats treated with guanethidine increases resorption in the mandibular bone surface [Hill et al, 1991]. In contrast, when guanethidine is administered to adult rats, the number of mononuclear pre-osteoclast(s), tartrate-resistant acid phosphatase-positive (TRAPþ) cells [Cherruau et al, 1999], as well as bone resorption pits [Cherruau et al, 2003], are reduced in the mandibular cortex subjected to synchronized resorption by molar(s) extraction. Other authors [Haug and Heyeraas, 2003], using a similar experimental model, found that surgical sympathectomy increases osteoclastic activity in the mandible, but not in the maxilla suggesting a site-specific response of bones to sympathectomy.…”