Mechanical deformation inhibits IL-10 and stimulates IL-12 production by mouse calvarial osteoblasts in vitro

García-López, Salvador; Meikle, Murray C.; Villanueva, Rosina; Montaño, Luis F.; Massó, Felipe; Ramírez‐Amador, Velia; Bojalil, Rafael

doi:10.1016/j.archoralbio.2004.09.001

Cited by 21 publications

(13 citation statements)

References 21 publications

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“…We have previously shown that cyclic mechanical strain in the same model system inhibits IL-10 and stimulates IL-12 production by mouse calvarial osteoblasts (28), two cytokines with the ability to inhibit bone resorption. IL-10 selectively blocks osteoclastogenesis by inhibiting the differentiation of osteoclast progenitors into preosteoclasts (41, 42), while IL-12 inhibits RANKL-induced osteoclast formation in mouse bone marrow cell cultures, an effect mediated by IFN-γ (43, 44).…”

Section: Discussionmentioning

confidence: 99%

“…Vacuum pressure was used to displace the substrate – maximal deflection 2 mm, according to the method of Banes et al (27) and a cyclic strain applied to the cells for 6 s (0.166 Hz), every 90 s for 2–48 h as described previously (28). The maximal strain applied to the cells was calculated according to the formula:

A r c MathClass-rel= \frac{1}{2} \sqrt{d^{2} MathClass-bin+ 16 b^{2}} MathClass-bin+ \frac{d^{2}}{8 b} 1 n ((), 4 b MathClass-bin+ \frac{\sqrt{d^{2} MathClass-bin+ 16 b^{2}}}{d})

d = diameter (33 mm); b = maximum deflection (2 mm); Arc = 33.23 mm

normalmax normalstrain MathClass-rel= \frac{A r c MathClass-bin- d}{d} 100 MathClass-rel= 0 MathClass-punc. 69 % MathClass-punc.

…”

Section: Methodsmentioning

confidence: 99%

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Alterations in the Synthesis of IL-1β, TNF-α, IL-6, and Their Downstream Targets RANKL and OPG by Mouse Calvarial Osteoblasts In vitro: Inhibition of Bone Resorption by Cyclic Mechanical Strain

2013

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Mechanical strain is an important determinant of bone mass and architecture, and the aim of this investigation was to further understand the role of the cell–cell signaling molecules, IL-1β, TNF-α, and IL-6 in the mechanobiology of bone. Mouse calvarial osteoblasts in monolayer culture were subjected to a cyclic out-of-plane deformation of 0.69% for 6 s, every 90 s for 2–48 h, and the levels of each cytokine plus their downstream targets RANKL and OPG measured in culture supernatants by ELISAs. Mouse osteoblasts constitutively synthesized IL-1β, TNF-α, and IL-6, the production of which was significantly up-regulated in all three by cyclic mechanical strain. RANKL and OPG were also constitutively synthesized; mechanical deformation however, resulted in a down-regulation of RANKL and an up-regulation OPG synthesis. We next tested whether the immunoreactive RANKL and OPG were biologically active in an isolated osteoclast resorption pit assay – this showed that culture supernatants from mechanically deformed cells significantly inhibited osteoclast-mediated resorptive activity across the 48 h time-course. These findings are counterintuitive, because IL-1β, TNF-α, and IL-6 have well-established reputations as bone resorptive agents. Nevertheless, they are pleiotropic molecules with multiple biological activities, underlining the complexity of the biological response of osteoblasts to mechanical deformation, and the need to understand cell–cell signaling in terms of cytokine networks. It is also important to recognize that osteoblasts cultured in vitro are deprived of the mechanical stimuli to which they are exposed in vivo – in other words, the cells are in a physiological default state that in the intact skeleton leads to decreased bone strains below the critical threshold required to maintain normal bone structure.

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Section: Discussionmentioning

confidence: 99%

A r c MathClass-rel= \frac{1}{2} \sqrt{d^{2} MathClass-bin+ 16 b^{2}} MathClass-bin+ \frac{d^{2}}{8 b} 1 n ((), 4 b MathClass-bin+ \frac{\sqrt{d^{2} MathClass-bin+ 16 b^{2}}}{d})

d = diameter (33 mm); b = maximum deflection (2 mm); Arc = 33.23 mm

normalmax normalstrain MathClass-rel= \frac{A r c MathClass-bin- d}{d} 100 MathClass-rel= 0 MathClass-punc. 69 % MathClass-punc.

…”

Section: Methodsmentioning

confidence: 99%

Alterations in the Synthesis of IL-1β, TNF-α, IL-6, and Their Downstream Targets RANKL and OPG by Mouse Calvarial Osteoblasts In vitro: Inhibition of Bone Resorption by Cyclic Mechanical Strain

2013

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“…Interleukin‐12 and IFN‐γ are integral regulators of the immune system and promote the development of Th1 cells whilst suppressing the Th2 phenotype (20,35,36). Like many cytokines, IFN‐γ and interleukin‐12 also play a role in bone metabolism (11,37–40). The results of our study indicate that alveolar bone destruction is significantly increased in the absence of either interleukin‐12p40 or IFN‐γ.…”

Section: Discussionmentioning

confidence: 99%

Alveolar bone loss in T helper 1/T helper 2 cytokine‐deficient mice

Alayan

Ivanovski

Farah

2006

J of Periodontal Research

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“…A number of other cytokines have been reported to regulate bone cell behavior. Interleukin‐7 (78) and IL‐10 (71) have an inhibitory action on osteoblast differentiation. Interleukin‐4 and IL‐13 are known to inhibit osteoblast differentiation (251), and mice over‐expressing IL‐4 appear to have a decreased bone formation, owing to a reduction in the number and activity of bone‐lining osteoblasts (145).…”

Section: Effects Of Inflammatory Cytokines On Osteoblast Differentiationmentioning

confidence: 99%

Effects of growth factors and cytokines on osteoblast differentiation

Hughes¹,

Turner²,

Belibasakis³

et al. 2006

Periodontology 2000

212

182

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Mechanical deformation inhibits IL-10 and stimulates IL-12 production by mouse calvarial osteoblasts in vitro

Cited by 21 publications

References 21 publications

Alterations in the Synthesis of IL-1β, TNF-α, IL-6, and Their Downstream Targets RANKL and OPG by Mouse Calvarial Osteoblasts In vitro: Inhibition of Bone Resorption by Cyclic Mechanical Strain

Alterations in the Synthesis of IL-1β, TNF-α, IL-6, and Their Downstream Targets RANKL and OPG by Mouse Calvarial Osteoblasts In vitro: Inhibition of Bone Resorption by Cyclic Mechanical Strain

Alveolar bone loss in T helper 1/T helper 2 cytokine‐deficient mice

Effects of growth factors and cytokines on osteoblast differentiation

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