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Review
. 2019 Apr 18;20(8):1919.
doi: 10.3390/ijms20081919.

The Endocannabinoid/Endovanilloid System in Bone: From Osteoporosis to Osteosarcoma

Francesca Rossi  1 , Chiara Tortora  2 , Francesca Punzo  3   4 , Giulia Bellini  5 , Maura Argenziano  6 , Alessandra Di Paola  7 , Marco Torella  8 , Silverio Perrotta  9
Affiliations
Review

The Endocannabinoid/Endovanilloid System in Bone: From Osteoporosis to Osteosarcoma

Francesca Rossi et al. Int J Mol Sci. .

Abstract

Bone is a dynamic tissue, whose homeostasis is maintained by a fine balance between osteoclast (OC) and osteoblast (OB) activity. The endocannabinoid/endovanilloid (EC/EV) system's receptors are the cannabinoid receptor type 1 (CB1), the cannabinoid receptor type 2 (CB2), and the transient receptor potential cation channel subfamily V member 1 (TRPV1). Their stimulation modulates bone formation and bone resorption. Bone diseases are very common worldwide. Osteoporosis is the principal cause of bone loss and it can be caused by several factors such as postmenopausal estrogen decrease, glucocorticoid (GC) treatments, iron overload, and chemotherapies. Studies have demonstrated that CB1 and TRPV1 stimulation exerts osteoclastogenic effects, whereas CB2 stimulation has an anti-osteoclastogenic role. Moreover, the EC/EV system has been demonstrated to have a role in cancer, favoring apoptosis and inhibiting cell proliferation. In particular, in bone cancer, the modulation of the EC/EV system not only reduces cell growth and enhances apoptosis but it also reduces cell invasion and bone pain in mouse models. Therefore, EC/EV receptors may be a useful pharmacological target in the prevention and treatment of bone diseases. More studies to better investigate the biochemical mechanisms underlining the EC/EV system effects in bone are needed, but the synthesis of hybrid molecules, targeting these receptors and capable of oppositely regulating bone homeostasis, seems to be a promising and encouraging prospective in bone disease management.

Keywords: CB1; CB2; TRPV1; bone; osteoblasts; osteoclasts; osteoporosis; osteosarcoma.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Signaling molecules involved in bone mass maintenance. The cannabinoid receptor type 1 (CB1), the cannabinoid receptor type 2 (CB2), and the transient receptor potential cation channel subfamily V member 1 (TRPV1) contribute to the maintenance of bone mass. CB2 receptor acts as inductor of bone matrix deposition, whereas the TRPV1 and CB1 receptors act as inhibitor of osteogenic signaling. M-CSF, Macrophage colony stimulating factor.
Figure 2
Figure 2
Altered homeostasis in osteoporosis. Activated osteoclasts (OCs) in patients with osteoporosis express low levels of CB2 receptor and high levels of CB1 and TRPV1. CB1 and TRPV1 stimulation activates osteoclasts, while CB2 represents the counterpart for bone mineralization and remodeling via osteoclast inhibition.
Figure 3
Figure 3
Representation of the multinucleated tartrate-resistant acid phosphatase (TRAP) (+) osteoclasts obtained by colorimetric assay (TRAP assay). The figure shows that osteoclasts (in purple) derived from (B) a postmenopausal woman with osteoporosis and from (C) an osteosarcoma patient are more active, as shown by the more intense staining and the larger size, with respect to osteoclasts derived from (A) a healthy donor.
See this image and copyright information in PMC

References

    1. Abdelgawad M.E., Delaisse J.M., Hinge M., Jensen P.R., Alnaimi R.W., Rolighed L., Engelholm L.H., Marcussen N., Andersen T.L. Early reversal cells in adult human bone remodeling: Osteoblastic nature, catabolic functions and interactions with osteoclasts. Histochem. Cell Biol. 2016;145:603–615. doi: 10.1007/s00418-016-1414-y. - DOI - PubMed
    1. Florencio-Silva R., Sasso G.R., Sasso-Cerri E., Simoes M.J., Cerri P.S. Biology of Bone Tissue: Structure, Function, and Factors That Influence Bone Cells. BioMed Res. Int. 2015;2015:421746. doi: 10.1155/2015/421746. - DOI - PMC - PubMed
    1. Xu Q., Chen G., Liu X., Dai M., Zhang B. Icariin inhibits RANKL-induced osteoclastogenesis via modulation of the NF-kappaB and MAPK signaling pathways. Biochem. Biophys. Res. Commun. 2019;508:902–906. doi: 10.1016/j.bbrc.2018.11.201. - DOI - PubMed
    1. Schneeweis L.A., Willard D., Milla M.E. Functional dissection of osteoprotegerin and its interaction with receptor activator of NF-kappaB ligand. J. Biol. Chem. 2005;280:41155–41164. doi: 10.1074/jbc.M506366200. - DOI - PubMed
    1. Luo J., Yang Z., Ma Y., Yue Z., Lin H., Qu G., Huang J., Dai W., Li C., Zheng C., et al. LGR4 is a receptor for RANKL and negatively regulates osteoclast differentiation and bone resorption. Nat. Med. 2016;22:539–546. doi: 10.1038/nm.4076. - DOI - PubMed

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