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.

Highlights

  • The cranberry (Vaccinium macrocarpon), a native North American fruit, has been widely investigated for its diverse beneficial effects for human health, primarily those related to its antiadherence activity [1]

  • This study suggests that AC-PACs can interfere with osteoclastic cell maturation and physiology as well as prevent bone resorption

  • Our laboratory showed that AC-PACs were able to inhibit matrix metalloproteinase (MMP) production by human macrophages stimulated with Aggregatibacter actinomycetemcomitans lipopolysaccharide (LPS), as well as to reduce matrix metalloproteinases (MMPs)-1 and -9 catalytic activities [7]

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Summary

Introduction

The cranberry (Vaccinium macrocarpon), a native North American fruit, has been widely investigated for its diverse beneficial effects for human health, primarily those related to its antiadherence activity [1]. Cranberry A-type proanthocyanidins (AC-PACs) demonstrated anti-adhesion effect against Escherichia coli, whereas B-type proanthocyanidins from other fruits were devoid of anti-adhesion properties [2,3]. Proanthocyanidin-enriched cranberry extracts have presented a variety of potential benefits for oral health, such as inhibition of biofilm formation and acid production by cariogenic bacteria [4] as well as modulation of the inflammatory response to periodontopathogens [5] and inactivation of bacteria-related proteolytic enzymes [6]. We have demonstrated that AC-PACs efficiently neutralized Porphyromonas gingivalis virulence properties and modulated the inflammatory response of epithelial cells to this periodontopathogen [8]

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