title: Galnon, a galanin receptor agonist, improves intrinsic cortical bone tissue properties but exacerbates bone loss in an ovariectomised rat model.
abstract: OBJECTIVE
  Previous studies have shown galanin (GAL) injections onto mouse calvaria increased bone thickness and osteoblast number. This study investigated the effects of the GAL receptor agonist galnon on bone loss using the ovariectomised (OVX) rat model.
  
  
  METHODS
  OVX rats were treated with either vehicle or galnon for 6 weeks via mini-osmotic pumps. Plasma osteocalcin concentrations, osseous cell gene expression, morphological and biomechanical properties of the skeleton were compared between the two groups.
  
  
  RESULTS
  Treatment with galnon increased RANKL:OPG gene ratio (p<0.001) plus expression of TNF-α (p<0.05) and cathepsin K (p<0.05). μCT analyses revealed galnon-treated OVX animals had reduced trabecular and cortical morphology compared to control animals. Biomechanically, galnon OVX animals required similar peak force to failure to that of control OVX animals although galnon treatment did enhance the mechanical properties of Young's modulus and ultimate tensile stress.
  
  
  CONCLUSIONS
  Our research suggests that galnon, a GAL receptor agonist, may enhance osteoclastic bone resorption in OVX rats. Although galnon reduced bone volume, biomechanical testing revealed that bone of galnon-treated animals was mechanically superior per unit area. Taken together, galnon simultaneously improves the intrinsic quality of cortical bone whilst stimulating osteoclastic activity in the OVX rat model.
authors.affiliation: La Trobe University, Department of Human Biosciences, La Trobe University, Bundoora, Australia.
authors.forename: H W
authors.initials: HW
authors.lastname: McGowan
authors.forename: J A
authors.initials: JA
authors.lastname: Schuijers
authors.forename: B L
authors.initials: BL
authors.lastname: Grills
authors.forename: S J
authors.initials: SJ
authors.lastname: McDonald
authors.forename: A C
authors.initials: AC
authors.lastname: McDonald
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D001842:Bone and Bones / Q000187:drug effects*; D003374:Coumarins / Q000494:pharmacology*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D015663:Osteoporosis, Postmenopausal; D010052:Ovariectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D044088:Receptors, Galanin / Q000819:agonists; D055114:X-Ray Microtomography
chemical_list: C456547:7-((9-fluorenylmethoxycarbonyl)cyclohexylalanyllysyl)amino-4-methylcoumarin; D050071:Bone Density Conservation Agents; D003374:Coumarins; D044088:Receptors, Galanin