Polarization Behavior of Bone Macrophage as Well as Associated Osteoimmunity in Glucocorticoid-Induced Osteonecrosis of the Femoral Head

Abstract

Glucocorticoid-induced osteonecrosis of the femoral head (GIONFH) is a disabling disease with high mortality in China but the detailed molecular and cellular mechanisms remain to be investigated. Macrophages are considered the key cells in osteoimmunology, and the cross-talk between bone macrophages and other cells in the microenvironment is involved in maintaining bone homeostasis. M1 polarized macrophages launch a chronic inflammatory response and secrete a broad spectrum of cytokines (eg, TNF-α, IL-6 and IL-1β) and chemokines to initiate a chronic inflammatory state in GIONFH. M2 macrophage is the alternatively activated anti-inflammatory type distributed mainly in the perivascular area of the necrotic femoral head. In the development of GIONFH, injured bone vascular endothelial cells and necrotic bone activate the TLR4/NF-κB signal pathway, promote dimerization of PKM2 and subsequently enhance the production of HIF-1, inducing metabolic transformation of macrophage to the M1 phenotype. Considering these findings, putative interventions by local chemokine regulation to correct the imbalance between M1/M2 polarized macrophages by switching macrophages to an M2 phenotype, or inhibiting the adoption of an M1 phenotype appear to be plausible regimens for preventing or intervening GIONFH in the early stage. However, these results were mainly obtained by in vitro tissue or experimental animal model. Further studies to completely elucidate the alterations of the M1/M2 macrophage polarization and functions of macrophages in glucocorticoid-induced osteonecrosis of the femoral head are imperative.

Precisely Regulating M2 Subtype Macrophages for Renal Fibrosis Resolution

“…Dex exerts potent anti-inflammatory effects. It acts on M cells to promote M1 to M2c polarization by inhibiting inflammation signaling pathways, including NF-κB . Additionally, by directly inhibiting TGF-βR1 and Smad3 activity, Dex can decrease M2 cell polarization, reduce probability of MMT cells conversion.…”

“…It acts on M cells to promote M1 to M2c polarization by inhibiting inflammation signaling pathways, including NF-κB. 48 Additionally, by directly inhibiting TGF-βR1 and Smad3 activity, 49 Dex can decrease M2 cell polarization, reduce probability of MMT cells conversion. ERS has been shown to play a significant role in renal fibrosis, 50 as evidenced by the high expression of the ER stress-related protein GRP78 observed in the immunofluorescence section of renal tissue isolated from UUO mice (Figure 2A).…”

m6A methylation modification and immune infiltration analysis in osteonecrosis of the femoral head

“…Previous studies reported that the immune inflammatory response generated by immune cell infiltration involved the disease process of ONFH [32,33]. Therefore, we explored the differences between two m6A subtypes in various immune cells.…”

Toll-like receptors in cardiac hypertrophy

“…Then, TRAF6 can activate NF-κB through TGF-β activated kinase 1 (TAK1) and MAPKs, such as JNK, extracellular-signal-regulated kinase (ERK), and p38 kinase, through mitogen-activated protein kinase ERKA 6 (MKK6), which, in turn, activates AP-1, leading to the expression of proinflammatory cytokines ( 51 , 85 – 87 ). Several different inflammatory cytokines, including TNF-α, IL-6, and IL-1β, are induced through this signaling pathway ( 88 ). For example, retinol-binding protein 4 (RBP4) contributes to insulin resistance and heart failure by activating the TLR4/MyD88 signaling pathway ( 49 ).…”