Low dose of propranolol down‐modulates bone resorption by inhibiting inflammation and osteoclast differentiation
- 9 March 2012
- journal article
- Published by Wiley in British Journal of Pharmacology
- Vol. 165 (7), 2140-2151
- https://doi.org/10.1111/j.1476-5381.2011.01686.x
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-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. 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. Low doses of propranolol suppress bone resorption by inhibiting RANKL-mediated osteoclastogenesis as well as inflammatory markers without affecting haemodynamic parameters.This publication has 51 references indexed in Scilit:
- Guide to Receptors and Channels (GRAC), 5th editionBritish Journal of Pharmacology, 2011
- Can a chronic dental infection be considered a cause of cardiovascular disease? A review of the literatureInternational Journal of Cardiology, 2011
- Combined treatment with a β-blocker and intermittent PTH improves bone mass and microarchitecture in ovariectomized miceBone, 2006
- Dose Effects of Propranolol on Cancellous and Cortical Bone in Ovariectomized Adult RatsThe Journal of pharmacology and experimental therapeutics, 2006
- Effects of β-adrenergic agonists on bone-resorbing activity in human osteoclast-like cellsBiochimica et Biophysica Acta (BBA) - Molecular Cell Research, 2003
- Adrenergic regulation of bone metabolism: Possible involvement of sympathetic innervation of osteoblastic and osteoclastic cellsMicroscopy Research and Technique, 2002
- NFAT Signaling: Choreographing the Social Lives of CellsCell, 2002
- Association Between Acute Cerebrovascular Ischemia and Chronic and Recurrent InfectionStroke, 1997
- Poor Oral Health and Coronary Heart DiseaseJournal of Dental Research, 1996
- Molecular Cloning of Human cDNA for Cathepsin K: Novel Cysteine Proteinase Predominantly Expressed in BoneBiochemical and Biophysical Research Communications, 1995