B. abortus Infection Promotes an Imbalance in the Adipocyte–Osteoblast Crosstalk Favoring Bone Resorption

Abstract

Osteoarticular injury is the most common presentation of active brucellosis in humans. Osteoblasts and adipocytes originate from mesenchymal stem cells (MSC). Since those osteoblasts are bone-forming cells, the predilection of MSC to differentiate into adipocytes or osteoblasts is a potential factor involved in bone loss. In addition, osteoblasts and adipocytes can be converted into each other according to the surrounding microenvironment. Here, we study the incumbency of B. abortus infection in the crosstalk between adipocytes and osteoblasts during differentiation from its precursors. Our results indicate that soluble mediators present in culture supernatants from B. abotus-infected adipocytes inhibit osteoblast mineral matrix deposition in a mechanism dependent on the presence of IL-6 with the concomitant reduction of Runt-related transcription factor 2 (RUNX-2) transcription, but without altering organic matrix deposition and inducing nuclear receptor activator ligand kβ (RANKL) expression. Secondly, B. abortus-infected osteoblasts stimulate adipocyte differentiation with the induction of peroxisome proliferator-activated receptor γ (PPAR-γ) and CCAAT enhancer binding protein β (C/EBP-β). We conclude that adipocyte–osteoblast crosstalk during B. abortus infection could modulate mutual differentiation from its precursor cells, contributing to bone resorption.

Extracellular Proteins Isolated from L. acidophilus as an Osteomicrobiological Therapeutic Agent to Reduce Pathogenic Biofilm Formation, Regulate Chronic Inflammation, and Augment Bone Formation In Vitro

“…Osteoblasts and bone marrow adipocytes are derived from the same progenitor cell (i.e., BMSCs), and a switch in lineage commitment toward adipogenic differentiation at the expense of osteoblastogenesis has been identified during bacterial infection, [77] and is a major contributor to various pathological bone diseases and tissue loss. [46,78,79] Here, we investigate the effect of LaEPs on both hBMSC osteogenic and adipogenic differentiation.…”

Sphingolipid-Induced Bone Regulation and Its Emerging Role in Dysfunction Due to Disease and Infection

“…As such, bacterial-targeted adipose dysfunction and use as a reservoir for pathogens could promote virulence, exacerbate infection, and ultimately result in bone loss. To this end, a switch in lineage commitment toward adipogenic differentiation at the expense of osteoblastogenesis and increased bone marrow adiposity has also been identified during bacterial infection [ 74 , 88 ]. Notably, bacteria including Staphylococcus aureus and Escherichia coli are able to adhere and internalize within adipose-derived MSCs, and the subsequent up- or downregulation of osteogenic versus adipogenic differentiation was observed to be dependent on the type of bacterial strain [ 89 ].…”