title: Disuse induced by botulinum toxin affects the bone marrow expression profile of bone genes leading to a rapid bone loss.
abstract: OBJECTIVE
  Molecular events occurring in the bone marrow microenvironment of an immobilized mouse limb after Botulinum toxin (BTX) injection haven't been characterized. BTX injection induces a localized disuse in which the tissue events have well been characterized.
  
  
  METHODS
  BTX injection was performed in the right quadriceps; saline injection in the left side was used as control. Mice were sacrificed at 0, 7, 14, 21 and 28 days; tibias were used for microCT analysis; bone marrow from femurs for RT-PCR analysis.
  
  
  RESULTS
  MicroCT revealed bone loss and microarchitectural damages on the immobilized side as from 7d; cortical area tended to be lower on the immobilized limb at 28d. Gene expression of formation factors was altered as from 7 days post-BTX: alkaline phosphatase, Tgfβ1, Lrp5, Sfrp2. Only Sfrp2 and Lrp5 were maintained altered until 28d. Expression of Dkk1 increased from 21d and represented a late inhibitor of formation. Gene expression of resorption markers increased as from 7d (Rankl, Tracp, Il1α, Il1β and Il6) and was maintained until 28d for Tracp and Il6.
  
  
  CONCLUSIONS
  A localized disuse induces rapid modifications in the bone marrow gene expression leading to bone loss due to an early decrease of formation associated with an increase in resorption.
authors: LUNAM Universite, GEROM - LHEA Groupe d'Etudes Remodelage Osseux et bioMateriaux, IRIS-IBS Institut de Biologie en Sante, CHU d'Angers, 49933 ANGERS Cedex, France. helene.marchand-libouban@univ-angers.fr
authors: H
authors: H
authors: Marchand-Libouban
authors: M A
authors: MA
authors: Le Drévo
authors: D
authors: D
authors: Chappard
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000473:pathology / Q000502:physiology*; D001862:Bone Resorption / Q000139:chemically induced* / Q000235:genetics* / Q000473:pathology; D001905:Botulinum Toxins / Q000633:toxicity*; D005260:Female; D051379:Mice; D020966:Muscular Disorders, Atrophic / Q000139:chemically induced* / Q000235:genetics* / Q000473:pathology; D052097:Quadriceps Muscle / Q000187:drug effects / Q000473:pathology; D059467:Transcriptome / Q000235:genetics
chemical_list: D001905:Botulinum Toxins