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Low dose of propranolol down‐modulates bone resorption by inhibiting inflammation and osteoclast differentiation

Rodrigues, WF ; Madeira, MFM ; da Silva, TA ; Clemente‐Napimoga, JT ; Miguel, CB ; Dias‐da‐Silva, VJ ; Barbosa‐Neto, O ; Lopes, AH ; Napimoga, MH

British journal of pharmacology, 2012-04, Vol.165 (7), p.2140-2151 [Periódico revisado por pares]

Oxford, UK: Blackwell Publishing Ltd

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Título:
Low dose of propranolol down‐modulates bone resorption by inhibiting inflammation and osteoclast differentiation
Autor: Rodrigues, WF ; Madeira, MFM ; da Silva, TA ; Clemente‐Napimoga, JT ; Miguel, CB ; Dias‐da‐Silva, VJ ; Barbosa‐Neto, O ; Lopes, AH ; Napimoga, MH
Assuntos: Acid Phosphatase - antagonists & inhibitors ; Acid Phosphatase - genetics ; Alveolar Bone Loss - prevention & control ; Animals ; Biological and medical sciences ; bone ; Bone Resorption - drug therapy ; Bone Resorption - metabolism ; Bone Resorption - pathology ; Cathepsin K - genetics ; Cell Differentiation - drug effects ; Cell Line ; Collagen Type I - metabolism ; Dose-Response Relationship, Drug ; Facial bones, jaws, teeth, parodontium: diseases, semeiology ; Gene Expression - drug effects ; Gingiva - drug effects ; Gingiva - metabolism ; Hemodynamics - drug effects ; inflammation ; Inflammation - prevention & control ; Intercellular Adhesion Molecule-1 - metabolism ; Interleukin-1beta - metabolism ; Isoenzymes - antagonists & inhibitors ; Isoenzymes - genetics ; Male ; Matrix Metalloproteinase 9 - genetics ; Medical sciences ; Mice ; NFATC Transcription Factors - antagonists & inhibitors ; Osteoclasts - drug effects ; Osteoclasts - pathology ; Otorhinolaryngology. Stomatology ; Peptides - metabolism ; periodontal disease ; Pharmacology. Drug treatments ; propranolol ; Propranolol - administration & dosage ; RANK Ligand - metabolism ; Rats ; Rats, Wistar ; Research Papers ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; Tartrate-Resistant Acid Phosphatase ; Transcription Factor RelA - metabolism ; Tumor Necrosis Factor-alpha - metabolism ; β‐blocker
É parte de: British journal of pharmacology, 2012-04, Vol.165 (7), p.2140-2151
Notas: ObjectType-Article-2
SourceType-Scholarly Journals-1
ObjectType-Feature-1
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Descrição: BACKGROUND AND PURPOSE 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. EXPERIMENTAL APPROACH 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 AND IMPLICATIONS Low doses of propranolol suppress bone resorption by inhibiting RANKL‐mediated osteoclastogenesis as well as inflammatory markers without affecting haemodynamic parameters.
Editor: Oxford, UK: Blackwell Publishing Ltd
Idioma: Inglês

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Low dose of propranolol down‐modulates bone resorption by inhibiting inflammation and osteoclast differentiation

Rodrigues, WF ; Madeira, MFM ; da Silva, TA ; Clemente‐Napimoga, JT ; Miguel, CB ; Dias‐da‐Silva, VJ ; Barbosa‐Neto, O ; Lopes, AH ; Napimoga, MH

Oxford, UK: Blackwell Publishing Ltd

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