High glutamate levels in the bone marrow of multiple myeloma patients promote osteoclast formation: a novel target for osteolytic bone disease.

ABSTRACT: Multiple Myeloma (MM) is a glutamine (Gln)-addicted cancer. Consequently, the MM bone microenvironment (BM) is characterized by lower Gln and higher glutamate (Glu) levels than those in pre-malignant monoclonal gammopathies. Such MM-dependent metabolic perturbation impairs osteoblast differentiation in the bone microenvironment, but its effect on osteoclast (OCL) bone resorption is still unknown. We first show that bone marrow mononuclear cells from MM patients release higher levels of Glu compared to those from patients with monoclonal gammopathy of undetermined significance (MGUS) or smoldering multiple myeloma (SMM). This increased Glu production correlates with elevated bone resorption activity. We then demonstrate that Glu stimulates OCL differentiation via the activation of NF-κB-NFA

SUBMITTER: Toscani D 

PROVIDER: S-EPMC12463672 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature