Juxtacrine interaction of macrophages and bone marrow stromal cells induce interleukin-6 signals and promote cell migration

Abstract

The bone marrow contains a heterogeneous milieu of cells, including macrophages, which are key cellular mediators for resolving infection and inflammation. Macrophages are most well known for their ability to phagocytose foreign bodies or apoptotic cells to maintain homeostasis; however, little is known about their function in the bone microenvironment. In the current study, we investigated the in vitro interaction of murine macrophages and bone marrow stromal cells (BMSCs), with focus on the juxtacrine induction of IL-6 signaling and the resultant effect on BMSC migration and growth. The juxtacrine interaction of primary mouse macrophages and BMSCs activated IL-6 signaling in the co-cultures, which subsequently enhanced BMSC migration and increased BMSC numbers. BMSCs and macrophages harvested from IL-6 knockout mice revealed that IL-6 signaling was essential for enhancement of BMSC migration and increased BMSC numbers via juxtacrine interactions. BMSCs were the main contributor of IL-6 signaling, and hence activation of the IL-6/gp130/STAT3 pathway. Meanwhile, macrophage derived IL-6 remained important for the overall production of IL-6 protein in the co-cultures. Taken together, these findings show the function of macrophages as co-inducers of migration and growth of BMSCs, which could directly influence bone formation and turnover.

Bone formation: Immune cell interactions promote growth

Immune cells in the bone marrow promote bone formation via interactions with other cells, with implications for bone healing and disease. This insight comes from work by Laurie K McCauley and colleagues at the Michigan School of Dentistry, USA, that focused on macrophages, a type of immune cell that destroys pathogens and dead cells. The researchers showed that the physical interactions of mouse macrophages with other cells in the bone marrow, known as bone marrow stromal cells, stimulated production of interleukin-6, a signaling molecule that is involved in bone formation. The increased production of interleukin-6 promoted growth and migration of the bone marrow stromal cells, thereby promoting bone formation. The findings suggest that macrophages are important for stimulation of bone growth during healing of fractures and could be important in understanding bone diseases such as osteoporosis.

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