ABSTRACT
Title
Deletion of TRPV1 gene decreases osteoclast activity and protects from ovariectomy-induced bone loss
Authors
S. Mancusi
Doctorate School in Pharmacological Sciences and Experimental and Clinical Medicine.
Department of Experimental Medicine, Section of Pharmacology - Second University of Naples, Italy
Doctorate School in Pharmacological Sciences and Experimental and Clinical Medicine.
Department of Experimental Medicine, Section of Pharmacology - Second University of Naples, Italy
Abstract
Transient receptor potential vanilloid type 1 (TRPV1) protein is a non-selective cation channel that belongs to the large family of TRP ion channels. TRPV1 is very frequently co-expressed with cannabinoid receptors (namely, CB1 and CB2) in neural cells, non-neural cells, osteoblasts, osteoclasts, and their precursors,and they share some of their endogenous agonists, anandamide (AEA) and N-arachidonoyl-dopamine [1].
TRPV1, CB1 and CB2 receptors together with the enzymatic machinery for the AEA metabolism represent the endovanilloid/endocannabinoid (EV/EC) system. Recently, an important role for the EV/EC system in the regulation of skeletal remodelling in human has been shown [2].
Skeleton is a highly specialized and metabolically active tissue that undergoes continuous remodeling throughout life. It is generally recognized that removal of bone is the task of osteoclasts (OCs), while its neo-formation relies on osteoblasts [3].
To assess the role of the TRPV1 channels in the regulation of bone mass we analysed the component of the EV/EC system and of the osteoclast activity marker TRAP in mice deficient for the TRPV1. Indeed, we show that TRPV1 deletion causes a drastic reduction of TRAP levels together with an significant increase of CB2 receptors expression and protects against ovariectomy-induced bone loss.
The absence of TRPV1 confirms that this receptor-signalling contributes to the loss of bone mass by direct stimulation of osteoclasts and counteracting the CB2 signalling that, on the other hand, contributes to the maintenance of bone mass directly stimulating osteoblasts and inhibiting osteoclasts. To the highlight of these data TRPV1 signalling seems to operate in mice as it has been demonstrated to act in humans and so these data suggest an important regulatory role of the EC/EV system in bone and new molecular targets for the development of diagnostic and therapeutic approaches to osteoporosis [3].
1) van der Eerden BC et al (2005)-The epithelial Ca2+ channel TRPV5 is essential for proper osteoclastic bone resorption.PNAS 102:17507-12.
2) Rossi F et al (2010)-The endovanilloid/endocannabinoid system in human osteoclasts: possible involvement in bone formation and resorption. Bone 44:476-84.
3) Rossi F et al (2011) The endovanilloid/endocannabinoid system: A new potential target for osteoporosis therapy. Bone in press.
TRPV1, CB1 and CB2 receptors together with the enzymatic machinery for the AEA metabolism represent the endovanilloid/endocannabinoid (EV/EC) system. Recently, an important role for the EV/EC system in the regulation of skeletal remodelling in human has been shown [2].
Skeleton is a highly specialized and metabolically active tissue that undergoes continuous remodeling throughout life. It is generally recognized that removal of bone is the task of osteoclasts (OCs), while its neo-formation relies on osteoblasts [3].
To assess the role of the TRPV1 channels in the regulation of bone mass we analysed the component of the EV/EC system and of the osteoclast activity marker TRAP in mice deficient for the TRPV1. Indeed, we show that TRPV1 deletion causes a drastic reduction of TRAP levels together with an significant increase of CB2 receptors expression and protects against ovariectomy-induced bone loss.
The absence of TRPV1 confirms that this receptor-signalling contributes to the loss of bone mass by direct stimulation of osteoclasts and counteracting the CB2 signalling that, on the other hand, contributes to the maintenance of bone mass directly stimulating osteoblasts and inhibiting osteoclasts. To the highlight of these data TRPV1 signalling seems to operate in mice as it has been demonstrated to act in humans and so these data suggest an important regulatory role of the EC/EV system in bone and new molecular targets for the development of diagnostic and therapeutic approaches to osteoporosis [3].
1) van der Eerden BC et al (2005)-The epithelial Ca2+ channel TRPV5 is essential for proper osteoclastic bone resorption.PNAS 102:17507-12.
2) Rossi F et al (2010)-The endovanilloid/endocannabinoid system in human osteoclasts: possible involvement in bone formation and resorption. Bone 44:476-84.
3) Rossi F et al (2011) The endovanilloid/endocannabinoid system: A new potential target for osteoporosis therapy. Bone in press.