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.