Glycolytic reprogramming in macrophages and MSCs during inflammation

Background Dysregulated inflammation is associated with many skeletal diseases and disorders, such as osteolysis, non-union of fractures, osteonecrosis, osteoarthritis orthopaedic infections. We previously showed that continuous infusion lipopolysaccharide (LPS) contaminated polyethylene particles (cPE) caused prolonged impaired bone formation. However, the metabolic bioenergetic processes are unknown. Mitochondria highly dynamic organelles modulate cell metabolism orchestrate inflammatory responses involve both resident recruited cells. Glycolytic reprogramming, shift from oxidative phosphorylation (OXPHOS) to glycolysis causes inappropriate activation function, resulting in dysfunctional cellular metabolism. hypothesized immunoregulation regeneration states glycolytic reprogramming mitochondrial dysfunction macrophages (Mφ) mesenchymal stromal cells (MSCs). Methods used Seahorse XF96 analyzer real-time qPCR study bioenergetics Mφ MSCs exposed cPE. To understand oxygen consumption rate (OCR), we XF Cell Mito Stress Test Kit analyzer. Similarly, Rate Assay was detect extracellular acidification (ECAR) Real-Time ATP kit production rates OXPHOS glycolysis. Real-time performed analyze gene expression key enzymes biogenesis. further detected proinflammatory cytokines genes related differentiation MSC during challenge Results Our results demonstrated cPE significantly decreased when compared control group. found reduced basal, maximal ATP-production coupled respiration rates, proton leak Meanwhile, increased basal efflux (PER) The percentage (%) PER higher cPE, indicating contribution pathway total elevated In line OCR ECAR, (glycoATP) lower (mitoATP) which mainly OXPHOS. Interestingly, enhanced but no significant changes (OCR). accordance, seahorse assay revealed glycoATP were while mitoATP differences Furthermore, upregulated levels regulators expressed pro-inflammatory cytokines. Conclusion This activity marrow-derived could impair immunoregulatory properties niche. underlying molecular defect disordered function represent a potential therapeutic target resolution inflammation.