title: Low dose of propranolol down-modulates bone resorption by inhibiting inflammation and osteoclast differentiation.
abstract: OBJECTIVE
  Bones are widely innervated, suggesting an important role for the sympathetic regulation of bone metabolism, although there are controversial studies. We investigated the effects of propranolol in a model of experimental periodontal disease.
  
  
  METHODS
  Rats were assigned as follows: animals without ligature; ligated animals receiving vehicle and ligated animals receiving 0.1, 5 or 20 mg·kg(-1) propranolol. After 30 days, haemodynamic parameters were measured by cardiac catheterization. Gingival tissues were removed and assessed for IL-1β, TNF-α and cross-linked carboxyterminal telopeptides of type I collagen (CTX) by elisa, or intercellular adhesion molecule 1 (ICAM-1), receptor activator of NF-κ B ligand (RANKL) and osteoprotegerin (OPG) by Western blot analysis. Sections from the mandibles were evaluated for bone resorption. Also, we analysed the ability of propranolol to inhibit osteoclastogenesis in vitro.
  
  
  RESULTS
  Propranolol at 0.1 and 5 mg·kg(-1) reduced the bone resorption as well as ICAM-1 and RANKL expression. However, only 0.1 mg·kg(-1) reduced IL-1β, TNF-α and CTX levels as well as increased the expression of OPG, but did not alter any of the haemodynamic parameters. Propranolol also suppressed in vitro osteoclast differentiation and resorptive activity by inhibiting the nuclear factor of activated T cells (NFATc)1 pathway and the expression of tartrate-resistant acid phosphatase (TRAP), cathepsin K and MMP-9.
  
  
  CONCLUSIONS
  Low doses of propranolol suppress bone resorption by inhibiting RANKL-mediated osteoclastogenesis as well as inflammatory markers without affecting haemodynamic parameters.
authors.affiliation: Laboratory of Biopathology and Molecular Biology, University of Uberaba, Uberaba, MG, Brazil.
authors.forename: W F
authors.initials: WF
authors.lastname: Rodrigues
authors.forename: M F M
authors.initials: MF
authors.lastname: Madeira
authors.forename: T A
authors.initials: TA
authors.lastname: da Silva
authors.forename: J T
authors.initials: JT
authors.lastname: Clemente-Napimoga
authors.forename: C B
authors.initials: CB
authors.lastname: Miguel
authors.forename: V J
authors.initials: VJ
authors.lastname: Dias-da-Silva
authors.forename: O
authors.initials: O
authors.lastname: Barbosa-Neto
authors.forename: A H
authors.initials: AH
authors.lastname: Lopes
authors.forename: M H
authors.initials: MH
authors.lastname: Napimoga
mesh_terms: D000135:Acid Phosphatase / Q000037:antagonists & inhibitors / Q000235:genetics; D016301:Alveolar Bone Loss / Q000517:prevention & control; D000818:Animals; D001862:Bone Resorption / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D056657:Cathepsin K / Q000235:genetics; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D024042:Collagen Type I / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000187:drug effects; D005881:Gingiva / Q000187:drug effects / Q000378:metabolism; D006439:Hemodynamics / Q000187:drug effects; D007249:Inflammation / Q000517:prevention & control; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000235:genetics; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D051379:Mice; D050778:NFATC Transcription Factors / Q000037:antagonists & inhibitors; D010010:Osteoclasts / Q000187:drug effects* / Q000473:pathology; D010455:Peptides / Q000378:metabolism; D011433:Propranolol / Q000008:administration & dosage*; D053245:RANK Ligand / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D000071681:Tartrate-Resistant Acid Phosphatase; D051996:Transcription Factor RelA / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D024042:Collagen Type I; D053583:Interleukin-1beta; D007527:Isoenzymes; D050778:NFATC Transcription Factors; D010455:Peptides; D053245:RANK Ligand; D012333:RNA, Messenger; C498144:Rela protein, mouse; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; C052929:collagen type I trimeric cross-linked peptide; D018799:Intercellular Adhesion Molecule-1; D011433:Propranolol; D000135:Acid Phosphatase; C000605511:Acp5 protein, mouse; D000071681:Tartrate-Resistant Acid Phosphatase; D056657:Cathepsin K; C534132:Ctsk protein, mouse; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse