Role of Muramyl Dipeptide in Lipopolysaccharide-Mediated Biological Activity and Osteoclast Activity

Abstract

Lipopolysaccharide (LPS) is an endotoxin and bacterial cell wall component that is capable of inducing inflammation and immunological activity. Muramyl dipeptide (MDP), the minimal essential structural unit responsible for the immunological activity of peptidoglycans, is another inflammation-inducing molecule that is ubiquitously expressed by bacteria. Several studies have shown that inflammation-related biological activities were synergistically induced by interactions between LPS and MDP. MDP synergistically enhances production of proinflammatory cytokines that are induced by LPS exposure. Injection of MDP induces lethal shock in mice challenged with LPS. LPS also induces osteoclast formation and pathological bone resorption; MDP enhances LPS induction of both processes. Furthermore, MDP enhances the LPS-induced receptor activator of NF-κB ligand (RANKL) expression and toll-like receptor 4 (TLR4) expression both in vivo and in vitro. Additionally, MDP enhances LPS-induced mitogen-activated protein kinase (MAPK) signaling in stromal cells. Taken together, these findings suggest that MDP plays an important role in LPS-induced biological activities. This review discusses the role of MDP in LPS-mediated biological activities, primarily in relation to osteoclastogenesis.

C‑X‑C receptor 7 agonist acts as a C‑X‑C motif chemokine ligand 12 inhibitor to ameliorate osteoclastogenesis and bone resorption

“…LPS induces RANKL expression from osteoblasts and production of proinflammatory cytokines, such as TNF-α and IL-1, from macrophages and other cells ( 37 ). It has been reported that periodontal ligament cells also express numerous types of proinflammatory cytokines to regulate osteoclastogenesis by LPS ( 38 ).…”

BCG-Induced Trained Immunity in Healthy Individuals: The Effect of Plasma Muramyl Dipeptide Concentrations

“…Since this lack of effect was independent of plasma-derived factors, it has been suggested that a cellular or cell-derived component from the blood is responsible for the inhibition of MDP in whole blood [19]. Furthermore, although MDP alone cannot induce immunoglobulin production [20], it is able to enhance expression of cell adhesion molecules and cytokines [14]. Moreover, several studies show increased production of proinflammatory cytokines upon MDP stimulation in vitro, also in synergy with other stimuli, which seem to depend on species and cell types used [14,19,21,22].…”

Effect of echinalkamide identified from Echinacea purpurea (L.) Moench on the inhibition of osteoclastogenesis and bone resorption

“…This activates transcription factors such as nuclear factor kappa B (NF-κB), activator protein-1 (AP1) and NFATc1, which are the subsequent genes of TRAF6, resulting in activation of p38, JNK and extracellular-signal regulated kinases (ERK). Activation is carried out at the protein level through phosphorylation processes including mitogen-activated protein kinases (MAPKs) and Phosphatidyl-inositol-3-kinase (PI3K)/Akt pathway 60,61 . Many studies have revealed that MAPKs can be stimulated by RANKL stimulation and are associated with osteoclastogenesis [62][63][64][65] .…”