title: Sympathetic nervous system does not mediate the load-induced cortical new bone formation.
abstract: The contribution of the SNS to bone's response to mechanical loading is unclear. Using a noninvasive model of axial loading of the murine tibia, we found that sciatic neurectomy enhances load-induced new cortical bone formation and that pharmacological blockade of the SNS does not affect such responses, indicating that the SNS does not mediate the osteogenic effects of loading in cortical bone.
  
  
  BACKGROUND
  There is increasing evidence that the sympathetic nervous system (SNS) contributes to the regulation of bone mass and may influence remodeling by modulating bones' response to mechanical load-bearing. The aim of this study was to examine the effect of sciatic neurectomy (SN) on the changes in cortical bone formation induced in response to mechanical loading and to investigate whether the SNS is directly involved in such load-induced responses.
  
  
  METHODS
  Accordingly, load-induced responses were compared in tibias of growing and adult control C57Bl/J6 mice and in mice submitted to unilateral SN; noninvasive axial loading that induced 2,000 microstrain on the tibia lateral midshaft cortex was applied cyclically, 5 or 100 days after surgery, for 7 minutes, 3 days/week for 2 weeks, and mice received calcein on the third and last days of loading. Tibias were processed for histomorphometry, and transverse confocal images from diaphyseal sites were analyzed to quantify new cortical bone formation. Chemical SNS inactivation was achieved by prolonged daily treatment with guanethidine sulfate (GS) or by the introduction of propranolol in drinking water.
  
  
  RESULTS
  Our results show that new cortical bone formation is enhanced by loading in all tibial sites examined and that load-induced periosteal and endosteal new bone formation was greater in the SN groups compared with sham-operated controls. This SN-related enhancement in load-induced cortical bone formation in tibias was more pronounced 100 days after neurectomy than after 5 days, suggesting that longer periods of immobilization promote a greater sensitivity to loading. In contrast, the increases in new bone formation induced in response to mechanical loading were similar in mice treated with either GS or propranolol compared with controls, indicating that inactivation of the SNS has no effect on load-induced cortical new bone formation.
  
  
  CONCLUSIONS
  This study shows that SN, or the absence of loading function it entails, enhances loading-related new cortical bone formation in the tibia independently of the SNS.
authors.affiliation: Department of Veterinary Basic Sciences, Royal Veterinary College, London, United Kingdom.
authors.forename: Roberto L
authors.initials: RL
authors.lastname: de Souza
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Pitsillides
authors.forename: Lance E
authors.initials: LE
authors.lastname: Lanyon
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Skerry
authors.forename: Chantal
authors.initials: C
authors.lastname: Chenu
mesh_terms: D000818:Animals; D003714:Denervation; D005260:Female; D006145:Guanethidine / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D010012:Osteogenesis / Q000187:drug effects / Q000502:physiology*; D010521:Periosteum / Q000187:drug effects / Q000254:growth & development / Q000294:innervation; D011433:Propranolol / Q000494:pharmacology; D012584:Sciatic Nerve / Q000601:surgery; D013564:Sympathetic Nervous System / Q000502:physiology*; D013977:Tibia / Q000187:drug effects / Q000254:growth & development / Q000294:innervation; D016474:Weight-Bearing / Q000502:physiology
chemical_list: D011433:Propranolol; D006145:Guanethidine