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|Title:||Low dose of propranolol down-modulates bone resorption by inhibiting inflammation and osteoclast differentiation|
|Author:||Rodrigues, W. F.|
Madeira, M. F. M.
da Silva, T. A.
Clemente-Napimoga, J. T.
Miguel, C. B.
Dias-da-Silva, V. J.
Lopes, A. H.
Napimoga, M. H.
|Abstract:||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. 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-1 beta, TNF-alpha and cross-linked carboxyterminal telopeptides of type I collagen (CTX) by ELISA, or intercellular adhesion molecule 1 (ICAM-1), receptor activator of NF-kappa 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. 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-1 beta, TNF-alpha 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. Low doses of propranolol suppress bone resorption by inhibiting RANKL-mediated osteoclastogenesis as well as inflammatory markers without affecting haemodynamic parameters|
Osso e ossos
|Editor:||John Wiley & Sons|
|Citation:||British Journal Of Pharmacology. Wiley-blackwell, v. 165, n. 7, n. 2140, n. 2151, 2012.|
|Appears in Collections:||FOP - Artigos e Outros Documentos|
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