scholarly journals Role of the Endocannabinoid/Endovanilloid System in the Modulation of Osteoclast Activity in Paget’s Disease of Bone

2021 ◽  
Vol 22 (18) ◽  
pp. 10158
Author(s):  
Marco Paoletta ◽  
Antimo Moretti ◽  
Sara Liguori ◽  
Alessandra Di Paola ◽  
Chiara Tortora ◽  
...  

The role of the endocannabinoid/endovanilloid (EC/EV) system in bone metabolism has recently received attention. Current literature evidences the modulation of osteoclasts and osteoblasts through the activation or inhibition of cannabinoid receptors in various pathological conditions with secondary involvement of bone tissue. However, this role is still unclear in primary bone diseases. Paget’s disease of the bone (PDB) could be considered a disease model for analyzing the role of the EC/EV system on osteoclasts (OCs), speculating the potential use of specific agents targeting this system for managing metabolic bone disorders. The aim of the study is to analyze OCs expression of EC/EV system in patients with PDB and to compare OCs activity between this population and healthy people. Finally, we investigate whether specific agents targeting EC/EV systems are able to modulate OCs activity in this metabolic bone disorder. We found a significant increase in cannabinoid receptor type 2 (CB2) protein expression in patients with PDB, compared to healthy controls. Moreover, we found a significant reduction in multi-nucleated tartrate-resistant acid phosphatase (TRAP)–positive OCs and resorption areas after treatment with JWH-133. CB2 could be a molecular target for reducing the activity of OCs in PDB, opening new therapeutic scenarios for the management of this condition.

Rheumatology ◽  
1992 ◽  
Vol 31 (1) ◽  
pp. 35-39 ◽  
Author(s):  
J. Y. REGINSTER ◽  
A. M. JEUGMANS-HUYNEN ◽  
M. WOUTERS ◽  
N. SARLET ◽  
H. D. MCINTYRE ◽  
...  

Molecules ◽  
2021 ◽  
Vol 26 (9) ◽  
pp. 2665
Author(s):  
Gyeong Do Park ◽  
Yoon-Hee Cheon ◽  
So Young Eun ◽  
Chang Hoon Lee ◽  
Myeung Su Lee ◽  
...  

Osteoporosis is a systemic metabolic bone disorder that is caused by an imbalance in the functions of osteoclasts and osteoblasts and is characterized by excessive bone resorption by osteoclasts. Targeting osteoclast differentiation and bone resorption is considered a good fundamental solution for overcoming bone diseases. β-boswellic acid (βBA) is a natural compound found in Boswellia serrata, which is an active ingredient with anti-inflammatory, anti-rheumatic, and anti-cancer effects. Here, we explored the anti-resorptive effect of βBA on osteoclastogenesis. βBA significantly inhibited the formation of tartrate-resistant acid phosphatase-positive osteoclasts induced by receptor activator of nuclear factor-B ligand (RANKL) and suppressed bone resorption without any cytotoxicity. Interestingly, βBA significantly inhibited the phosphorylation of IκB, Btk, and PLCγ2 and the degradation of IκB. Additionally, βBA strongly inhibited the mRNA and protein expression of c-Fos and NFATc1 induced by RANKL and subsequently attenuated the expression of osteoclast marker genes, such as OC-STAMP, DC-STAMP, β3-integrin, MMP9, ATP6v0d2, and CtsK. These results suggest that βBA is a potential therapeutic candidate for the treatment of excessive osteoclast-induced bone diseases such as osteoporosis.


2021 ◽  
Vol 22 (22) ◽  
pp. 12374
Author(s):  
Federica Saponaro ◽  
Rebecca Ferrisi ◽  
Francesca Gado ◽  
Beatrice Polini ◽  
Alessandro Saba ◽  
...  

Novel interest has arisen in recent years regarding bone, which is a very complex and dynamic tissue deputed to several functions ranging from mechanical and protective support to hematopoiesis and calcium homeostasis maintenance. In order to address these tasks, a very refined, continuous remodeling process needs to occur involving the coordinated action of different types of bone cells: osteoblasts (OBs), which have the capacity to produce newly formed bone, and osteoclasts (OCs), which can remove old bone. Bone remodeling is a highly regulated process that requires many hormones and messenger molecules, both at the systemic and the local level. The whole picture is still not fully understood, and the role of novel actors, such as the components of the endocannabinoids system (ECS), including endogenous cannabinoid ligands (ECs), cannabinoid receptors (CBRs), and the enzymes responsible for endogenous ligand synthesis and breakdown, is extremely intriguing. This article reviews the connection between the ECS and skeletal health, supporting the potential use of cannabinoid receptor ligands for the treatment of bone diseases associated with accelerated osteoclastic bone resorption, including osteoporosis and bone metastasis.


2002 ◽  
Vol 172 (3) ◽  
pp. 673-681 ◽  
Author(s):  
M Jevon ◽  
A Sabokbar ◽  
Y Fujikawa ◽  
T Hirayama ◽  
SD Neale ◽  
...  

A number of bone diseases characterised by excessive osteolysis (e.g. osteoporosis and Paget's disease) exhibit a marked gender difference in prevalence and are more common in the elderly population. Bone resorption is carried out by osteoclasts, which are formed by fusion of circulating mononuclear precursor cells of haematopoietic origin. In this study, we have determined whether there are gender- and age-related differences in osteoclast formation from circulating precursors. Peripheral blood mononuclear cells (PBMCs) were co-cultured with UMR106 osteoblast-like cells in the presence of macrophage-colony stimulating factor (M-CSF) and 1,25 dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) or cultured alone in the presence of sRANKL (soluble receptor activator of nuclear factor kappa B ligand) and M-CSF. As assessed by the formation of tartrate resistant acid phosphatase (TRAP)-positive (TRAP(+)) and vitronectin receptor-positive (VNR(+)) multinucleated cells (MNCs), there was no difference in the number of circulating osteoclast precursors in males and females. Lacunar resorption carried out by osteoclasts formed from these precursors was generally increased in males compared with females (P=0.03). An increase in the number of TRAP(+) and VNR(+) MNCs formed from male PBMCs was noted in response to 1,25(OH)(2)D(3) (P<0.005). An increase in lacunar resorption in cultures of PBMCs (10(5) per well) from males was also noted in response to 10(-9) M 1,25(OH)(2)D(3) (P<0.05) and sRANKL (P=0.05), but not M-CSF. The addition of dexamethasone resulted in a marked increase in osteoclast formation and lacunar resorption in both males and females. Post-menopausal females and males of comparable age showed similar levels of osteoclastogenesis. Pre-menopausal women showed similar levels of osteoclastogenesis but less resorption (P=0.01) compared with males of comparable age. These results show that there are specific gender/age-related differences in osteoclast formation and bone resorption and have implications for evaluating osteoclastogenesis in skeletal diseases such as primary osteoporosis and Paget's disease.


Author(s):  
Navnit S. Makaram ◽  
Stuart H. Ralston

Abstract Purpose of Review To provide an overview of the role of genes and loci that predispose to Paget’s disease of bone and related disorders. Recent Findings Studies over the past ten years have seen major advances in knowledge on the role of genetic factors in Paget’s disease of bone (PDB). Genome wide association studies have identified six loci that predispose to the disease whereas family based studies have identified a further eight genes that cause PDB. This brings the total number of genes and loci implicated in PDB to fourteen. Emerging evidence has shown that a number of these genes also predispose to multisystem proteinopathy syndromes where PDB is accompanied by neurodegeneration and myopathy due to the accumulation of abnormal protein aggregates, emphasising the importance of defects in autophagy in the pathogenesis of PDB. Summary Genetic factors play a key role in the pathogenesis of PDB and the studies in this area have identified several genes previously not suspected to play a role in bone metabolism. Genetic testing coupled to targeted therapeutic intervention is being explored as a way of halting disease progression and improving outcome before irreversible skeletal damage has occurred.


Author(s):  
Richard W. Keen

♦ Avascular Necrosis♦ Paget’s disease♦ Transient Osteoporosis of the Hip.


Pathology ◽  
1996 ◽  
Vol 28 (3) ◽  
pp. 248-250 ◽  
Author(s):  
Raj K. Gupta ◽  
John Simpson ◽  
Carl Dowle

2006 ◽  
Vol 14 (3) ◽  
pp. 1020-1023 ◽  
Author(s):  
P. Sukumvanich ◽  
D. J. Bentrem ◽  
H. S. Cody III ◽  
E. Brogi ◽  
J. V. Fey ◽  
...  

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