Curcumin in Combination with Piperine Suppresses Osteoclastogenesis In Vitro

J Endod. 2015 Oct;41(10):1638-45. doi: 10.1016/j.joen.2015.05.009. Epub 2015 Aug 20.


Introduction: The dietary pigment curcumin is a natural polyphenol extracted from the Curcuma longa rhizomes native to South Asia. The antioxidative, antimicrobial, and anti-inflammatory activities besides its unknown side effects suggest that curcumin could be a promising antiresorptive agent to prevent replacement resorption in replanted teeth after traumatic avulsion. Piperine, an alkaloid present in black pepper, seems to enhance the bioavailability and activity of curcumin. Therefore, this study evaluated the biocompatibility of curcumin and piperine in cultures of periodontal ligament cells as well as their effects in an in vitro osteoclastogenesis model of RAW 264.7 macrophages.

Methods: The cytotoxicity in human periodontal ligament fibroblasts, human osteogenic sarcoma cells (SAOS-2), and murine osteoclastic precursors (RAW 264.7) was analyzed by using cell number determination and proliferation assays. The ability of curcumin and its conjugate to suppress the receptor activator of nuclear factor kappa B ligand-induced osteoclastogenesis was assessed by tartrate-resistant acid phosphatase (TRAP) staining and activity as well as real-time polymerase chain reaction.

Results: Curcumin at concentrations ≥ 10 μmol/L was cytotoxic in all cell types tested, whereas piperine showed only slight cytotoxicity at 30 μmol/L in RAW and SAOS cultures. Although curcumin caused already significant effects, the combination with piperine completely suppressed the osteoclastogenesis by decreasing the TRAP activity and inhibiting the expression of the specific osteoclast markers TRAP, cathepsin K, and calcitonin receptor.

Conclusions: We demonstrated that curcumin combined with piperine suppressed the osteoclastogenesis in vitro without causing cytotoxic effects in periodontal ligament cells. These findings suggest its potential therapeutic application for the prevention and treatment of replacement resorption in replanted avulsed teeth.

Keywords: Cytotoxicity, dental avulsion, osteoclast markers, osteoclastogenesis, RANKL, RAW 264.7, root resorption, TRAP activity.

MeSH terms

  • Alkaloids / pharmacology*
  • Animals
  • Benzodioxoles / pharmacology*
  • Cells, Cultured
  • Curcumin / pharmacology*
  • Fibroblasts / cytology
  • Fibroblasts / drug effects
  • Humans
  • Mice
  • Osteogenesis / drug effects*
  • Periodontal Ligament / cytology*
  • Piperidines / pharmacology*
  • Polyunsaturated Alkamides / pharmacology*
  • Postoperative Complications
  • RAW 264.7 Cells
  • Root Resorption / prevention & control
  • Root Resorption / therapy
  • Tooth Avulsion / surgery
  • Tooth Replantation / adverse effects


  • Alkaloids
  • Benzodioxoles
  • Piperidines
  • Polyunsaturated Alkamides
  • Curcumin
  • piperine