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Internalization of Mycobacterium bovis Bacillus Calmette‐Guérin into Osteoblast‐Like MC3T3‐E1 Cells and Bone Resorptive Responses of the Cells against the Infection

Mycobacterium bovis BCG (BCG) is a live vaccine used worldwide against tuberculosis. However, it has unfavourable side effects such as osteitis or osteomyelitis, and these sometimes lead to vertebral caries in some patients as a result of bone resorption. Osteoblasts might play a role in the bone resorption caused by BCG infection, because they are central cells in bone metabolism. Cultured osteoblast‐like cell lines (MC3T3‐E1) derived from C57BL mice susceptible to BCG infection cells were infected with BCG at several doses. Interestingly, internalization of BCG‐enveloped phagosome‐like membrane in osteoblast‐like cells were observed by transmission electron microscopy (TEM). Owing to infection, the proliferation and alkaline phosphatase activity of the osteoblast‐like cells were reduced in a dose‐dependent manner. On the other hand, interleukin (IL)‐6 production was considerably enhanced by infection. These results suggest that BCG infects osteoblasts, suppressing their proliferation and differentiation and inducing bone resorption, which may be related to osteitis/osteomyelitis and bone caries caused by BCG infection.