Interleukin 4, interferon-gamma, and prostaglandin E impact the osteoclastic cell-forming potential of murine bone marrow macrophages.

Abstract

Interleukin 4 (IL-4) is an immune cytokine that inhibits bone resorption in mice and suppresses osteoclastic cell formation in vitro through an undefined mechanism. In this report, we have established the cellular identity of the IL-4 target cell using a variety of bone marrow/stromal cell coculture methods. Initially, we found that the majority of IL-4's inhibition of osteoclastic cell formation was due to its effect on bone marrow cells, not stromal cells. Consequently, bone marrow macrophages were used as osteoclastic cell progenitors after they had been transiently exposed to IL-4 (48 h), before the addition of stromal cells, 1,25-dihydroxyvitamin D3, and dexamethasone. In this circumstance, IL-4 impaired subsequent osteoclastic cell formation, suggesting that the macrophage may be potentially targeted by many factors known to influence osteoclast formation. Consequently, we discovered that interferon-gamma (IFN gamma), prostaglandin E (PGE), and cell-permeant cAMP analogs also impacted osteoclastic cell formation when used to selectively treat bone marrow macrophages. IFN gamma suppressed osteoclastic cell formation, whereas PGE and cAMP analog treatment led to the formation of significantly enlarged osteoclastic cells. Importantly, PGE antagonized the inhibitory effects of both IL-4 and IFN gamma on the osteoclastic cell-forming potential of bone marrow macrophages. Collectively, these findings establish bone marrow macrophages as osteoclastic cell precursors with the degree of their commitment to the osteoclast pathway sensitive to the effects of soluble mediators, including IL-4, IFN gamma, and PGE.

osteoprotegerin-deficient mice develop early onset osteoporosis and arterial calcification

“…The levels of osteoclast precursors contained in OPG −/− or wild-type bone marrow and spleen cells were found to be similar when measured by an in vitro osteoclast-forming assay (Lacey et al 1995; data not shown). This finding suggests that the osteoporosis in OPG −/− mice is most likely due to dysregulated osteoclast recruitment and activation in vivo rather than alterations in the number of osteoclast precursors.…”

Anti IL‐17A therapy inhibits bone loss in TNF‐α‐mediated murine arthritis by modulation of the T‐cell balance

“…Most strikingly, a consistent signal towards Th2 differentiation was observed with increased expression of IL-4 in the LNs of hTNFtg mice suggesting a shift from the Th17 to the Th2 linage. This is interesting, as IL-4 is one of the most potent suppressors of osteoclast formation [25]. IL-4 inhibits osteoclast differentiation through directly activating PPARg [26], which is a potent transcriptional suppressor for osteoclast differentiation [27].…”

Pesquisa de interferon gama em tecido periodontal de ratos submetidos à movimentação dentária induzida

“…Alguns autores 7,10,12 afirmam que o INF-γ poderia suprimir a formação de osteoclastos por atuar em um período precoce de sua diferenciação. Choi e Kim 4 reforçaram essa afirmativa, ao assegurarem que o INF-γ atuaria diretamente sobre a FIGURA 3 -Representação esquemática das áreas periodontais demarcadas para análise microscópica: (A) área de pressão e (B) área de tração da raiz mesial do 1MS.…”

“…Citocinas como INF-γ e IL-4 podem suprimir a formação de osteoclastos, por atuarem sobre suas células precursoras -os macrófagos da medula ós-sea 12 . De acordo com Fox e Chambers 7 , o INF-γ evita a formação de osteoclastos por atuar diretamente na diferenciação de suas células progenitoras, levando-as à morte celular.…”

“…Com relação às células capazes de produzir o INF-γ, diversos autores 1,10,12,13 citam o linfócitos T e as células Natural Killers (NK) como responsá-veis pela produção dessa citocina. No entanto, essas células são pouco vistas no ligamento periodontal, mesmo em um processo inflamatório provocado pelos estresses mecânico e funcional do movimento ortodôntico.…”