BACKGROUND AND PURPOSEBones 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 APPROACHRats 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-1b, TNF-a and cross-linked carboxyterminal telopeptides of type I collagen (CTX) by ELISA, or intercellular adhesion molecule 1 (ICAM-1), receptor activator of NF-k 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. RESULTSPropranolol 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-1b, TNF-a 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 IMPLICATIONSLow doses of propranolol suppress bone resorption by inhibiting RANKL-mediated osteoclastogenesis as well as inflammatory markers without affecting haemodynamic parameters. AbbreviationsAP, arterial pressure; BD, bone density; CTX, cross-linked carboxyterminal telopeptides of type I collagen; DMEM, Dulbecco's modified Eagle medium; DTT, dithiothreitol; FBS, fetal bovine serum; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; ICAM-1, intercellular adhesion molecule 1; LVEDP, left ventricular end-diastolic pressure; LVSP, left ventricular systolic pressure; NFAT, nuclear factor of activated T cells; OPG, osteoprotegerin; OVX, ovariectomized; RANKL, receptor activator of NF-k B ligand; SaM-1, human periosteum-derived osteoblastic cells; SaOS-2, human osteosarcoma-derived cells; SHR, spontaneous hypertensive rats; TBST, Tris-buffered saline-Tween; TRAP, tartrate-resistant acid phosphatase BJP British Journal of Pharmacology