Characterization of the bone-resorptive effect of interleukin-11 in cultured mouse calvarial bones

Åhlén, Jan; Andersson, S.; Mukohyama, Hitoshi; Roth, C.; Bäckman, Assar; Conaway, H. Herschel; Lerner, Ulf H.

doi:10.1016/s8756-3282(02)00784-6

Cited by 57 publications

(44 citation statements)

References 38 publications

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“…Exogenous addition of OPG will also inhibit the calvarial bone-resorptive response of IL-11 (58). In the present study, three additional members of the IL-6 family of cytokines, IL-6 (plus sIL-6R), LIF, and OSM, were found to be good stimulators of resorption in neonatal mouse calvarial bones.…”

Section: Discussionsupporting

confidence: 48%

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IL-6, Leukemia Inhibitory Factor, and Oncostatin M Stimulate Bone Resorption and Regulate the Expression of Receptor Activator of NF-κB Ligand, Osteoprotegerin, and Receptor Activator of NF-κB in Mouse Calvariae

Palmqvist

Persson

Conaway

et al. 2002

The Journal of Immunology

444

315

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IL-6, leukemia inhibitory factor (LIF), and oncostatin M (OSM) are IL-6-type cytokines that stimulate osteoclast formation and function. In the present study, the resorptive effects of these agents and their regulation of receptor activator of NF-κB ligand (RANKL), RANK, and osteoprotegerin (OPG) were studied in neonatal mouse calvaria. When tested separately, neither human (h) IL-6 nor the human soluble IL-6R (shIL-6R) stimulated bone resorption, but when hIL-6 and the shIL-6R were combined, significant stimulation of both mineral and matrix release from bone explants was noted. Semiquantitative RT-PCR showed that hIL-6 plus shIL-6R enhanced the expression of RANKL and OPG in calvarial bones, but decreased RANK expression. Human LIF, hOSM, and mouse OSM (mOSM) also stimulated 45Ca release and enhanced the mRNA expression of RANKL and OPG in mouse calvaria, but had no effect on the expression of RANK. In agreement with the RT-PCR analyses, ELISA measurements showed that both hIL-6 plus shIL-6R and mOSM increased RANKL and OPG proteins. 1,25-Dihydroxyvitamin D3 (D3) also increased the RANKL protein level, but decreased the protein level of OPG. OPG inhibited 45Ca release stimulated by RANKL, hIL-6 plus shIL-6R, hLIF, hOSM, mOSM, and D3. An Ab neutralizing mouse gp130 inhibited 45Ca release induced by hIL-6 plus shIL-6R. These experiments demonstrated stimulation of calvarial bone resorption and regulation of mRNA and protein expression of RANKL and OPG by D3 and IL-6 family cytokines as well as regulation of RANK expression in preosteoclasts/osteoclasts of mouse calvaria by D3 and hIL-6 plus shIL-6R.

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Section: Discussionsupporting

confidence: 48%

“…Recent studies have shown that IL-11 stimulates RANKL and OPG mRNA expression in osteoblasts and mouse calvaria (58,59) without affecting the mRNA expression of RANK in the calvarial bones (58). Exogenous addition of OPG will also inhibit the calvarial bone-resorptive response of IL-11 (58).…”

Section: Discussionmentioning

confidence: 99%

IL-6, Leukemia Inhibitory Factor, and Oncostatin M Stimulate Bone Resorption and Regulate the Expression of Receptor Activator of NF-κB Ligand, Osteoprotegerin, and Receptor Activator of NF-κB in Mouse Calvariae

Palmqvist

Persson

Conaway

et al. 2002

The Journal of Immunology

444

315

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“…One microgram of RNA from MG-63 cells was reverse transcribed into single-stranded cDNA with a first-strand cDNA synthesis kit using random p(dN) 6 primers, and the cDNA was amplified utilizing a PCR core kit as previously described (34). For all genes, no amplification was detected in samples in which the reverse transcriptase reaction had been omitted (data not shown).…”

Section: Semiquantitative Reverse Transcription-pcr (Rt-pcr)mentioning

confidence: 98%

“…Quantitative real-time PCR. Analyses of messenger RNA (mRNA) expression with quantitative real-time PCR were performed using the TaqMan Universal PCR Master Mix kit (Applied Biosystems) as described in detail previously (34). Following DNase treatment, total RNA (0.5-1 g) was reverse transcribed into single-stranded cDNA using the first-strand cDNA synthesis kit with random p(dN) 6 primers.…”

Section: Semiquantitative Reverse Transcription-pcr (Rt-pcr)mentioning

confidence: 99%

Bradykinin potentiates cytokine‐induced prostaglandin biosynthesis in osteoblasts by enhanced expression of cyclooxygenase 2, resulting in increased RANKL expression

Brechter¹,

Lerner²

2007

Arthritis & Rheumatism

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Objective. Bradykinin (BK) stimulates bone resorption in vitro and synergistically potentiates interleukin-1 (IL-1)-induced bone resorption and prostaglandin (PG) formation, suggesting that kinins are important in inflammation-induced bone loss. The present study was undertaken to study 1) the role of the kinin B1 and B2 receptors in the synergistic interaction with IL-1 and tumor necrosis factor ␣ (TNF␣), 2) the molecular mechanisms involved in synergistic enhancement of PG formation, and 3) the effects of kinins on cytokine-induced expression of RANKL, RANK, and osteoprotegerin (OPG) (the latter being crucial molecules in osteoclast differentiation).Methods. Formation of PGs, expression of enzymes involved in arachidonic acid metabolism, and expression of RANKL, RANK, and OPG were assessed in the human osteoblastic cell line MG-63 and in mouse calvarial bones.

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“…Similarly, IL-11 induced RANKL expression in cultured mouse calvarial bones and stimulated bone resorption (Ahlen et al, 2002). The effect of various interleukins on osteoclastogenesis is summarized in Table 1.…”

Section: Regulation Of Osteoclast Differentiation By Interleukins Thamentioning

confidence: 98%

The Role of Jak/STAT Pathways in Osteoclast Differentiation

Lee¹,

Kim²

2011

Biomolecules and Therapeutics

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OSTEOCLASTOsteoclasts are the bone-resorbing cells of monocyte/macrophage origin (Boyle et al., 2003). In mice, CD45R -CD11b low bone marrow cells were identifi ed as osteoclast precursors at least in vitro (Jacquin et al., 2006). Mizoguchi et al. established that cell cycle arrest in osteoclast precursors is prerequisite for osteoclast differentiation (Mizoguchi et al., 2009). These cells were identifi ed as c-Fms + (M-CSF receptor) RANKL + cells at the site of osteoclastogenesis in vivo. Upon stimulation of these osteoclast precursors with macrophage colonystimulation factor (M-CSF) and receptor activator of nuclear factor kappa B ligand (RANKL), these cells differentiate and fi nally fuse to form multinuclear functional osteoclasts through a multi-step process. M-CSF supports the survival and proliferation of osteoclast precursors. The critical role of M-CSF in osteoclastogenesis was revealed by the osteopetrotic bone phenotype of op/op mice, which lack functional M-CSF leading to the absence of osteoclasts (Yoshida et al., 1990). Genetic ablation of RANKL also induced osteopetrosis accompanied by complete loss of osteoclasts (Kong et al., 1999). Ligation of RANKL receptor (RANK) by RANKL recruits TNF receptor associated factors (TRAFs) and stimulates NF-κB, c-Fos, and NFATc1-mediated gene transcription by activating multiple signaling cascades including mitogen-activated proOsteoclasts are bone-resorbing cells of monocyte/macrophage origin and are culprits of bone destruction associated with osteoporosis, rheumatoid arthritis, and cancer bone metastasis. Recent advances in osteoclast biology revealed central roles of various cytokines in regulating osteoclastogenesis both in vitro and in vivo. However, exact underlying mechanisms including signaling pathways downstream of receptor ligation are still under pursuit. In the present review, the role of Jak/STAT proteins and their regulators will be discussed in connection with osteoclastogenesis, since growing evidence indicates that a number of cytokines and growth factors utilizing Jak/STAT signaling pathways affect osteoclastogenesis. A better understanding on the role of Jak/ STAT pathways in osteoclast differentiation will not only strengthen our knowledge on osteoclast biology but also provide invaluable insights into the development of anti-resorptive strategies for treating bone-lytic diseases. Abstract tein kinases such as ERK, JNK, and p38 as well as phosphatidylinositol 3-kinase (PI3K)/Akt pathways (Lee and Kim, 2003). The major osteoclast signaling pathway is depicted in Fig.

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Characterization of the bone-resorptive effect of interleukin-11 in cultured mouse calvarial bones

Cited by 57 publications

References 38 publications

IL-6, Leukemia Inhibitory Factor, and Oncostatin M Stimulate Bone Resorption and Regulate the Expression of Receptor Activator of NF-κB Ligand, Osteoprotegerin, and Receptor Activator of NF-κB in Mouse Calvariae

IL-6, Leukemia Inhibitory Factor, and Oncostatin M Stimulate Bone Resorption and Regulate the Expression of Receptor Activator of NF-κB Ligand, Osteoprotegerin, and Receptor Activator of NF-κB in Mouse Calvariae

Bradykinin potentiates cytokine‐induced prostaglandin biosynthesis in osteoblasts by enhanced expression of cyclooxygenase 2, resulting in increased RANKL expression

The Role of Jak/STAT Pathways in Osteoclast Differentiation

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