Cannabinoids and Bone: Endocannabinoids modulate human osteoclast function in vitro

Lauren Sarah Whyte, L Ford, S A Ridge, G A Cameron, M J Rogers, R A Ross

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Background and purpose: Both CB(1) and CB(2) cannabinoid receptors have been shown to play a role in bone metabolism. Crucially, previous studies have focussed on the effects of cannabinoid ligands in murine bone cells. This study aimed to investigate the effects of cannabinoids on human bone cells in vitro. Experimental Approach: Quantitative RT-PCR was used to determine expression of cannabinoid receptors and liquid chromatography-electrospray ionisation tandem mass spectrometry was used to determine the presence of endocannabinoids in human bone cells. The effect of cannabinoids on human osteoclast formation, polarisation and resorption was determined by assessing the number of cells expressing a(v) ß(3) or with F-actin rings, or measurement of resorption area. Key Results: Human osteoclasts express both CB(1) and CB(2) receptors. CB(2) expression was significantly higher in human monocytes compared to differentiated osteoclasts. Furthermore, the differentiation of human osteoclasts from monocytes was associated with a reduction in 2-AG levels and an increase in AEA levels. Treatment of osteoclasts with LPS significantly increased levels of AEA. Nanomolar concentrations of AEA and the synthetic agonists CP 55,940 and JWH015 stimulated human osteoclast polarisation and resorption; these effects were attenuated in the presence of CB(1) and/or CB(2) antagonists. Conclusions and Implications: Low concentrations of cannabinoids activate human osteoclasts in vitro. There is a dynamic regulation of the expression of the CB(2) receptor and the production of the endocannabinoids during the differentiation of human bone cells. The data suggest that small molecules modulating the endocannabinoid system may be important therapeutics in human bone disease.
Original languageEnglish
Pages (from-to)2584-2597
Number of pages14
JournalBritish Journal of Pharmacology
Volume165
Issue number8
Early online date23 Mar 2012
DOIs
Publication statusPublished - Apr 2012

Fingerprint

Endocannabinoids
Cannabinoids
Osteoclasts
Bone and Bones
Cannabinoid Receptors
Monocytes
In Vitro Techniques
Electrospray Ionization Mass Spectrometry
Bone Diseases
Tandem Mass Spectrometry
Liquid Chromatography
Actins
Cell Count
Ligands
Polymerase Chain Reaction

Keywords

  • cannabinoid
  • CB1
  • CB2
  • Endocannabinoid
  • 2-AG
  • AEA
  • bone
  • osteocast
  • osteoblast
  • LPS

Cite this

Whyte, L. S., Ford, L., Ridge, S. A., Cameron, G. A., Rogers, M. J., & Ross, R. A. (2012). Cannabinoids and Bone: Endocannabinoids modulate human osteoclast function in vitro. British Journal of Pharmacology, 165(8), 2584-2597. https://doi.org/10.1111/j.1476-5381.2011.01519.x

Cannabinoids and Bone : Endocannabinoids modulate human osteoclast function in vitro. / Whyte, Lauren Sarah; Ford, L; Ridge, S A; Cameron, G A; Rogers, M J; Ross, R A.

In: British Journal of Pharmacology, Vol. 165, No. 8, 04.2012, p. 2584-2597.

Research output: Contribution to journalArticle

Whyte, LS, Ford, L, Ridge, SA, Cameron, GA, Rogers, MJ & Ross, RA 2012, 'Cannabinoids and Bone: Endocannabinoids modulate human osteoclast function in vitro' British Journal of Pharmacology, vol. 165, no. 8, pp. 2584-2597. https://doi.org/10.1111/j.1476-5381.2011.01519.x
Whyte, Lauren Sarah ; Ford, L ; Ridge, S A ; Cameron, G A ; Rogers, M J ; Ross, R A. / Cannabinoids and Bone : Endocannabinoids modulate human osteoclast function in vitro. In: British Journal of Pharmacology. 2012 ; Vol. 165, No. 8. pp. 2584-2597.
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AU - Ridge, S A

AU - Cameron, G A

AU - Rogers, M J

AU - Ross, R A

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N2 - Background and purpose: Both CB(1) and CB(2) cannabinoid receptors have been shown to play a role in bone metabolism. Crucially, previous studies have focussed on the effects of cannabinoid ligands in murine bone cells. This study aimed to investigate the effects of cannabinoids on human bone cells in vitro. Experimental Approach: Quantitative RT-PCR was used to determine expression of cannabinoid receptors and liquid chromatography-electrospray ionisation tandem mass spectrometry was used to determine the presence of endocannabinoids in human bone cells. The effect of cannabinoids on human osteoclast formation, polarisation and resorption was determined by assessing the number of cells expressing a(v) ß(3) or with F-actin rings, or measurement of resorption area. Key Results: Human osteoclasts express both CB(1) and CB(2) receptors. CB(2) expression was significantly higher in human monocytes compared to differentiated osteoclasts. Furthermore, the differentiation of human osteoclasts from monocytes was associated with a reduction in 2-AG levels and an increase in AEA levels. Treatment of osteoclasts with LPS significantly increased levels of AEA. Nanomolar concentrations of AEA and the synthetic agonists CP 55,940 and JWH015 stimulated human osteoclast polarisation and resorption; these effects were attenuated in the presence of CB(1) and/or CB(2) antagonists. Conclusions and Implications: Low concentrations of cannabinoids activate human osteoclasts in vitro. There is a dynamic regulation of the expression of the CB(2) receptor and the production of the endocannabinoids during the differentiation of human bone cells. The data suggest that small molecules modulating the endocannabinoid system may be important therapeutics in human bone disease.

AB - Background and purpose: Both CB(1) and CB(2) cannabinoid receptors have been shown to play a role in bone metabolism. Crucially, previous studies have focussed on the effects of cannabinoid ligands in murine bone cells. This study aimed to investigate the effects of cannabinoids on human bone cells in vitro. Experimental Approach: Quantitative RT-PCR was used to determine expression of cannabinoid receptors and liquid chromatography-electrospray ionisation tandem mass spectrometry was used to determine the presence of endocannabinoids in human bone cells. The effect of cannabinoids on human osteoclast formation, polarisation and resorption was determined by assessing the number of cells expressing a(v) ß(3) or with F-actin rings, or measurement of resorption area. Key Results: Human osteoclasts express both CB(1) and CB(2) receptors. CB(2) expression was significantly higher in human monocytes compared to differentiated osteoclasts. Furthermore, the differentiation of human osteoclasts from monocytes was associated with a reduction in 2-AG levels and an increase in AEA levels. Treatment of osteoclasts with LPS significantly increased levels of AEA. Nanomolar concentrations of AEA and the synthetic agonists CP 55,940 and JWH015 stimulated human osteoclast polarisation and resorption; these effects were attenuated in the presence of CB(1) and/or CB(2) antagonists. Conclusions and Implications: Low concentrations of cannabinoids activate human osteoclasts in vitro. There is a dynamic regulation of the expression of the CB(2) receptor and the production of the endocannabinoids during the differentiation of human bone cells. The data suggest that small molecules modulating the endocannabinoid system may be important therapeutics in human bone disease.

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