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

2019 ◽  
Vol 20 (8) ◽  
pp. 1919 ◽  
Author(s):  
Rossi ◽  
Tortora ◽  
Punzo ◽  
Bellini ◽  
Argenziano ◽  
...  
Keyword(s):  
Transient Receptor Potential ◽  
Cannabinoid Receptor ◽  
Bone Cancer ◽  
Receptor Potential ◽  
Bone Diseases ◽  
Receptor Type ◽  
Bone Homeostasis ◽  
Hybrid Molecules ◽  
Postmenopausal Estrogen ◽  
Transient Receptor

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.

scholarly journals URB597 abrogates anxiogenic and depressive behaviors in the methamphetamine-withdrawal mice: Role of the cannabinoid receptor type 1, cannabinoid receptor type 2, and transient receptor potential vanilloid 1 channels

2020 ◽  
pp. 026988112096593
Author(s):  
Mohaddeseh Ebrahimi-Ghiri ◽  
Fatemeh Khakpai ◽  
Mohammad-Reza Zarrindast
Keyword(s):  
Transient Receptor Potential ◽  
Cannabinoid Receptor ◽  
Endocannabinoid System ◽  
Receptor Potential ◽  
Receptor Type ◽  
Anxiety And Depression ◽  
Transient Receptor Potential Vanilloid ◽  
Transient Receptor

Background: Methamphetamine is an addictive stimulant that possesses toxicity in the brain when taken repeatedly or at higher doses. Methamphetamine neurotoxicity is associated with numerous forms of mental impairment, including depression and anxiety. Evidence has also demonstrated that the endocannabinoid system is involved in the regulation of anxiety and depression. Aims: This study was designed to determine the involvement of the endocannabinoid system in anxiety- and depression-related behaviors in methamphetamine-withdrawal male NMRI mice. Methods: The elevated plus maze and forced swim test were used to assess the level of anxiety and depression. Results: We found that methamphetamine (30 mg/kg, intraperitoneal) evoked depressive- and anxiogenic-like effects at 3 days post-administration. Injection of URB597 (5–10 ng/mouse, intracerebroventricular), 10 min before the test, prevented the emotional deficits induced by methamphetamine withdrawal. Moreover, the cannabinoid receptor type 1 antagonist AM251 (1 μg/mouse) or cannabinoid receptor type 2 antagonist AM630 (5 and 10 μg/mouse) suppressed the antidepressant activity in the methamphetamine-withdrawal mice treated with URB597. The transient receptor potential vanilloid 1 antagonist capsazepine (25 μg/mouse) prevented while capsazepine (100 μg/mouse) potentiated the antidepressant efficacy in the methamphetamine-withdrawal mice treated with URB597. The higher dose of AM630 and two higher doses of capsazepine had antidepressant efficacy, by themselves. Furthermore, capsazepine (50 μg/mouse) increased locomotion in the methamphetamine-withdrawal mice treated with URB597. Conclusions: The results suggest that URB597 has a potential for preventing methamphetamine withdrawal-evoked anxiety and depression. Cannabinoid type 1 receptors, cannabinoid type 2 receptors and transient receptor potential vanilloid 1 differently affect depression-related behaviors in methamphetamine-withdrawal mice treated with URB597.

Are Osteoclasts Mechanosensitive Cells?

2021 ◽  
Vol 17 (10) ◽  
pp. 1917-1938
Author(s):  
Qingxuan Wang ◽  
Mengmeng Duan ◽  
Jingfeng Liao ◽  
Jing Xie ◽  
Chenchen Zhou
Keyword(s):  
Transient Receptor Potential ◽  
Bone Cells ◽  
Receptor Potential ◽  
Binding Motif ◽  
Mechanical Forces ◽  
Bone Homeostasis ◽  
Physical Environments ◽  
Extracellular Compartment ◽  
Transient Receptor ◽  
Canonical Wnt

Skeleton metabolism is a process in which osteoclasts constantly remove old bone and osteoblasts form new osteoid and induce mineralization; disruption of this balance may cause diseases. Osteoclasts play a key role in bone metabolism, as osteoclastogenesis marks the beginning of each bone remodeling cycle. As the only cell capable of bone resorption, osteoclasts are derived from the monocyte/macrophage hematopoietic precursors that terminally adhere to mineralized extracellular matrix, and they subsequently break down the extracellular compartment. Bone is generally considered the load-burdening tissue, bone homeostasis is critically affected by mechanical conductions, and the bone cells are mechanosensitive. The functions of various bone cells under mechanical forces such as chondrocytes and osteoblasts have been reported; however, the unique bone-resorbing osteoclasts are less studied. The oversuppression of osteoclasts in mechanical studies may be because of its complicated differentiation progress and flexible structure, which increases difficulty in targeting mechanical structures. This paper will focus on recent findings regarding osteoclasts and attempt to uncover proposed candidate mechanosensing structures in osteoclasts including podosome-associated complexes, gap junctions and transient receptor potential family (ion channels). We will additionally describe possible mechanotransduction signaling pathways including GTPase ras homologue family member A (RhoA), Yes-associated protein/transcriptional co-activator with PDZ-binding motif (TAZ), Ca2+ signaling and non-canonical Wnt signaling. According to numerous studies, evaluating the possible influence of various physical environments on osteoclastogenesis is conducive to the study of bone homeostasis.

Sign in / Sign up

Export Citation Format

Share Document