The role of TNF-α and IFN-γ in the formation of osteoclasts and bone absorption in bone tuberculosis

Bone-joint tuberculosis is one lytic bone lesion caused by Tubercle bacilli. Tumor necrosis factor (TNF)-α interferon (IFN)-γ can mediate bone formation and osteoclasts. This study aimed to investigate the effect of these factors in the effect of Tubercle bacilli on osteoclast formation and bone absorption. Bone marrow mononuclear cells were separated and generated for osteoblast-osteoclast co-culture system. The effect of Mt sonicate on osteoclast formation and bone absorption was observed, with the correlation analysis between TNF-α and IFN-γ concentration. Real-time PCR was employed to detect mRNA expression of receptor activator NF-κB ligand (RANKL) and osteoprotegerin (OPG) in osteoblasts. Immunofluorescence was used to quantify NFATc1 protein level. Antibody against TNF-α and IFN-γ was applied for observing bone absorption. Mt sonicate significantly enhance osteoclast formation and bone absorption and facilitate secretion of TNF-α and IFN-γ. It can also elevate mRNA expression of RANKL and OPG in osteoblast and decrease NFATc1 in osteoclast. The block of TNF-α or IFN-γ significantly weaken Mt sonicate-induced osteoclast formation and bone absorption, facilitate OPG expression, and decrease RNAKL and NFATc1 expression. Tubercle bacilli induced release of TNF-α and IFN-γ is important for bone absorption. TNF-α and IFN-γ interfere the interaction between osteoclast and osteoblast, causing bone destruction, via the modulation on the expression of OPG and RANKL in osteoblast.