Primary human bone marrow adipocytes support TNF-α-induced osteoclast differentiation and function through RANKL expression
H Goto, A Hozumi, M Osaki, T Fukushima, K Sakamoto… - Cytokine, 2011 - Elsevier
H Goto, A Hozumi, M Osaki, T Fukushima, K Sakamoto, A Yonekura, M Tomita, K Furukawa…
Cytokine, 2011•ElsevierPURPOSE: In previous reports, it was demonstrated that bone marrow adipocytes were
related to steroid osteoporosis through osteoclastogenesis induced by Receptor Activator of
Nuclear factor κ-B Ligand (RANKL) expression. The purpose of this study was to evaluate
the effect of Tumor necrosis factor-alpha (TNF-α) on RANKL expression in bone marrow
adipocytes, and osteoclast differentiation supported by human bone marrow adipocytes.
METHODS: RANKL, osteoprotegerin (OPG), and macrophage-colony stimulating factor (M …
related to steroid osteoporosis through osteoclastogenesis induced by Receptor Activator of
Nuclear factor κ-B Ligand (RANKL) expression. The purpose of this study was to evaluate
the effect of Tumor necrosis factor-alpha (TNF-α) on RANKL expression in bone marrow
adipocytes, and osteoclast differentiation supported by human bone marrow adipocytes.
METHODS: RANKL, osteoprotegerin (OPG), and macrophage-colony stimulating factor (M …
PURPOSE
In previous reports, it was demonstrated that bone marrow adipocytes were related to steroid osteoporosis through osteoclastogenesis induced by Receptor Activator of Nuclear factor κ-B Ligand (RANKL) expression. The purpose of this study was to evaluate the effect of Tumor necrosis factor-alpha (TNF-α) on RANKL expression in bone marrow adipocytes, and osteoclast differentiation supported by human bone marrow adipocytes.
METHODS
RANKL, osteoprotegerin (OPG), and macrophage-colony stimulating factor (M-CSF) mRNA expression in bone marrow adipocytes and their regulation by TNF-α treatment were measured by real-time RT-PCR. Co-cultures of bone marrow adipocytes and osteoclast precursors were performed with or without TNF-α, and osteoclast differentiation was evaluated morphologically and functionally.
RESULTS
RANKL expression and an increase in the RANKL/OPG ratio in bone marrow adipocytes were stimulated by TNF-α treatment. In co-culture of bone marrow adipocytes and osteoclast precursors with TNF-α, the number of TRAP-positive multinuclear cells and resorption cavity formations of calcium phosphate film were increased. Osteoclast differentiation was suppressed by anti-RANKL antibody treatment. In co-culture with non-cell-contact conditions, no TRAP-positive cells or resorption cavity formations were observed.
CONCLUSIONS
TNF-α increased RANKL expression in primary human bone marrow adipocytes. TNF-α induced the ability of bone marrow adipocytes to promote osteoclast differentiation and activity in a manner directly related to RANKL expression.
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