The endovanilloid/endocannabinoid system in human osteoclasts: possible involvement in bone formation and resorption

Bone. 2009 Mar;44(3):476-84. doi: 10.1016/j.bone.2008.10.056. Epub 2008 Nov 14.

Abstract

Recent studies suggest a role for the endocannabinoid/endovanilloid anandamide in the regulation of bone resorption/formation balance in mice. Here, we examined the co-expression of the transient receptor potential vanilloid type 1 (TRPV1) and the cannabinoid CB1/CB2 receptors together with N-acylphosphatidylethanolamine-hydrolizing phospholipase D (NAPE-PLD) and fatty acid amide hydrolase (FAAH), the two enzymes responsible of the synthesis and catabolism of anandamide respectively, in human osteoclasts. Co-expression of TRPV1, CB1/CB2, NAPE-PLD and FAAH was found in both human osteoclast cultures and in native osteoclasts from human bone biopsies. Moreover, agonist-evoked calcium entry indicated that the TRPV1 receptor is functionally active in vitro. Consistently, biomolecular and functional experiments showed that resiniferatoxin (RTX), a selective TRPV1 receptor agonist, increased the expression and the activity of TRAP and cathepsin K, two specific osteoclast biomarkers. The evidence that cannabinoid and vanilloid receptors are co-expressed in human osteoclasts suggests that they might cross-talk to modulate the intrinsic balance of bone mineralization and resorption by different actions of anandamide through TRPV1 and cannabinoid receptors. The presence of the endocannabinoid/endovanilloid proteins in human osteoclasts will likely have implications for the management of bone demineralization associated syndrome (i. e. osteoporosis).

MeSH terms

  • Acid Phosphatase / genetics
  • Acid Phosphatase / metabolism
  • Amidohydrolases / metabolism
  • Animals
  • Arachidonic Acids / metabolism*
  • Bone Resorption*
  • Bone and Bones / cytology
  • Bone and Bones / metabolism
  • Calcium / metabolism
  • Cannabinoid Receptor Modulators / metabolism*
  • Capsaicin / metabolism
  • Cathepsin K
  • Cathepsins / metabolism
  • Cell Differentiation
  • Cells, Cultured
  • Endocannabinoids*
  • Humans
  • Isoenzymes / genetics
  • Isoenzymes / metabolism
  • Mice
  • Osteoclasts / cytology
  • Osteoclasts / physiology*
  • Osteogenesis / physiology*
  • Phospholipase D / metabolism
  • Polyunsaturated Alkamides / metabolism*
  • Receptor, Cannabinoid, CB1 / metabolism
  • Receptor, Cannabinoid, CB2 / metabolism
  • TRPV Cation Channels / metabolism
  • Tartrate-Resistant Acid Phosphatase

Substances

  • Arachidonic Acids
  • Cannabinoid Receptor Modulators
  • Endocannabinoids
  • Isoenzymes
  • Polyunsaturated Alkamides
  • Receptor, Cannabinoid, CB1
  • Receptor, Cannabinoid, CB2
  • TRPV Cation Channels
  • TRPV1 receptor
  • Acid Phosphatase
  • Acp5 protein, mouse
  • Tartrate-Resistant Acid Phosphatase
  • Phospholipase D
  • Cathepsins
  • CTSK protein, human
  • Cathepsin K
  • Ctsk protein, mouse
  • Amidohydrolases
  • fatty-acid amide hydrolase
  • Capsaicin
  • Calcium
  • anandamide