Marino_2020_Calcif.Tissue.Int_107_72

Reference

Title : JZL184, A Monoacylglycerol Lipase Inhibitor, Induces Bone Loss in a Multiple Myeloma Model of Immunocompetent Mice - Marino_2020_Calcif.Tissue.Int_107_72
Author(s) : Marino S , Carrasco G , Li B , Shah KM , Lath DL , Sophocleous A , Lawson MA , Idris AI
Ref : Calcif Tissue Int , 107 :72 , 2020
Abstract :

Multiple myeloma (MM) patients develop osteolysis characterised by excessive osteoclastic bone destruction and lack of osteoblast bone formation. Pharmacological manipulation of monoacylglycerol lipase (MAGL), an enzyme responsible for the degradation of the endocannabinoid 2-arachidonoyl glycerol (2-AG), reduced skeletal tumour burden and osteolysis associated with osteosarcoma and advanced breast and prostate cancers. MM and hematopoietic, immune and bone marrow cells express high levels of type 2 cannabinoid receptor and osteoblasts secrete 2-AG. However, the effects of MAGL manipulation on MM have not been investigated. Here, we report that treatment of pre-osteoclasts with non-cytotoxic concentrations of JZL184, a verified MAGL inhibitor, enhanced MM- and RANKL-induced osteoclast formation and size in vitro. Exposure of osteoblasts to JZL184 in the presence of MM cell-derived factors reduced osteoblast growth but had no effect on the ability of these cells to mature or form bone nodules. In vivo, administration of JZL184 induced a modest, yet significant, bone loss at both trabecular and cortical compartments of long bones of immunocompetent mice inoculated with the syngeneic 5TGM1-GFP MM cells. Notably, JZL184 failed to inhibit the in vitro growth of a panel of mouse and human MM cell lines, or reduce tumour burden in mice. Thus, MAGL inhibitors such as JZL184 can exacerbate MM-induced bone loss.

PubMedSearch : Marino_2020_Calcif.Tissue.Int_107_72
PubMedID: 32285169

Related information

Citations formats

Marino S, Carrasco G, Li B, Shah KM, Lath DL, Sophocleous A, Lawson MA, Idris AI (2020)
JZL184, A Monoacylglycerol Lipase Inhibitor, Induces Bone Loss in a Multiple Myeloma Model of Immunocompetent Mice
Calcif Tissue Int 107 :72

Marino S, Carrasco G, Li B, Shah KM, Lath DL, Sophocleous A, Lawson MA, Idris AI (2020)
Calcif Tissue Int 107 :72