Bacterial metabolite interference with differentiation of mouse bone marrow-derived osteoclasts.

초록

Bone turnover normally occurs in a highly regulated manner throughout life. It involves two different kinds of cells, osteoclasts and osteoblasts. Osteoclasts, the monocyte-macrophage lineage cells, resorb bone and osteoblasts deposit bone. Perturbations to these processes underlie skeletal disorders, such as osteoporosis. To understand the cellular and molecular mechanisms of bone biology and for the identification and characterization of new drug targets and therapies, a mouse co-culture system of osteoblasts and hematopoietic cells is established, in which osteoclasts are formed in response to 1 a ,25-dihydroxyvitamin D3 (1 a ,25(OH)₂D₃) and prostaglandin E₂ (PGE₂). Using this co-culture system, the bacterial metabolite n-butyrate, which has well-known anti-inflammatory effects, is shown to stimulate or inhibit osteoclastogenesis depending on the concentration. These results demonstrate a novel property of w-butyrate that may modulate osteoclastogenesis via osteoblasts.