title: A-type cranberry proanthocyanidins inhibit the RANKL-dependent differentiation and function of human osteoclasts.
abstract: This study investigated the effect of A-type cranberry proanthocyanidins (AC-PACs) on osteoclast formation and bone resorption activity. The differentiation of human pre-osteoclastic cells was assessed by tartrate-resistant acid phosphatase (TRAP) staining, while the secretion of interleukin-8 (IL-8) and matrix metalloproteinases (MMPs) was measured by ELISA. Bone resorption activity was investigated by using a human bone plate coupled with an immunoassay that detected the release of collagen helical peptides. AC-PACs up to 100 µg/mL were atoxic for osteoclastic cells. TRAP staining evidenced a dose-dependent inhibition of osteoclastogenesis. More specifically, AC-PACs at 50 µg/mL caused a 95% inhibition of RANKL-dependent osteoclast differentiation. This concentration of AC-PACs also significantly increased the secretion of IL-8 (6-fold) and inhibited the secretion of both MMP-2 and MMP-9. Lastly, AC-PACs (10, 25, 50 and 100 µg/ml) affected bone degradation mediated by mature osteoclasts by significantly decreasing the release of collagen helical peptides. This study suggests that AC-PACs can interfere with osteoclastic cell maturation and physiology as well as prevent bone resorption. These compounds may be considered as therapeutic agents for the prevention and treatment of periodontitis.
authors.affiliation: Groupe de Recherche en Écologie Buccale, Faculté de Médecine Dentaire, Université Laval, 2420 Rue de La Terrasse, Quebec City, QC G1V0A6, Canada.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Tanabe
authors.forename: Juliana
authors.initials: J
authors.lastname: Santos
authors.forename: Vu Dang
authors.initials: VD
authors.lastname: La
authors.forename: Amy B
authors.initials: AB
authors.lastname: Howell
authors.forename: Daniel
authors.initials: D
authors.lastname: Grenier
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects*; D044945:Proanthocyanidins / Q000302:isolation & purification / Q000494:pharmacology*; D053245:RANK Ligand / Q000037:antagonists & inhibitors* / Q000502:physiology; D029799:Vaccinium macrocarpon / Q000737:chemistry*
chemical_list: D044945:Proanthocyanidins; D053245:RANK Ligand; C505688:TNFSF11 protein, human