Interaction of Triiodothyronine With 1α,25-Dihydroxyvitamin D3 on Interleukin-6-Dependent Osteoclast-like Cell Formation in Mouse Bone Marrow Cell Cultures

Schiller, C; Gruber, Reinhard; Ho, Guan-Min; Redlich, Kurt; Gober, H.-J; Katzgraber, F.; Willheim, Martin; Hoffmann, Oskar; Pietschmann, Péter; Peterlik, Meinrad

doi:10.1016/s8756-3282(97)00291-3

Cited by 30 publications

(11 citation statements)

References 26 publications

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“…In fact, these two hormones have been shown to influence MC3T3-E1 cells at different levels, such as in the regulation of osteocalcin and matrix metalloproteinase-13 mRNA expression (35) and the molecular organization of adherens junctions among these osteblastic cells (36). Interaction of thyroid hormone with 1,25(OH) 2 VD was also shown in mouse bone marrow cell cultures, in which T 3 in combination with 1,25(OH) 2 VD, but not alone, induced osteoclastogenesis in a synergic manner (34).…”

Section: Discussionmentioning

confidence: 72%

“…Remarkably, D2 activity in MC3T3-E1 cells was not only stimulated by 1,25(OH) 2 VD but also was increased with time after cells were seeded, compatible with D2-generated T 3 playing a role in osteoblastic differentiation. In fact, it is known that thyroid hormone induces osteoblast differentiation (32,33) and increases osteoclastogenesis (34).…”

Section: Discussionmentioning

confidence: 99%

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Type 2 Iodothyronine Selenodeiodinase Is Expressed throughout the Mouse Skeleton and in the MC3T3-E1 Mouse Osteoblastic Cell Line during Differentiation

et al. 2005

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Thyroid hormone affects multiple aspects of bone metabolism, but little is known about thyroid hormone deiodination in bone cells except that cultures of skeletal cells and bone organ express types 1 and 2 iodothyronine deiodinases (D1 and D2) mRNAs. In the present study, outer ring deiodination (ORD) activity was detected in bone extracts of multiple sites of the mouse skeleton, bone marrow, and the MC3T3-E1 osteoblastic cell line. In all tissues, ORD was detected using 125I-rT3 or 125I-T4 as substrates and was found to be 6-n-propylthiouracil insensitive, display a Michaelis constant (T4) of approximately 1 nM, increase about 3-fold in hypo- and virtually disappear in thyrotoxicosis. Extracts of calvaria had the lowest ORD activity, whereas tibial and femoral extracts had roughly three times as much. The absence of ORD activity in bone extracts from mice with targeted disruption of the Dio2 gene confirms the principal role of D2 in this tissue. In the MC3T3-E1 osteoblasts, D2 activity increased in a time-dependent manner after plating, and with the content of selenium in the media, reaching a maximum 5-7 d later as cells attained more than 90% confluence. In these cells D2 half-life is about 30-40 min, which is further accelerated by exposure to substrate and stabilized by the proteasome inhibitor, MG132. Treatment with vitamin D [1,25(OH)2VD]-induced D2 activity by 2- to 3-fold as early as 24 h, regardless of the level of cell confluence, but estradiol, PTH, forskolin, leptin, TNFalpha, TGFbeta, and dexamethasone did not affect D2. Given the role of D2 in other cell types and processes, it is likely that bone ORD not only plays a role in bone development and adult bone T3 homeostasis but also contributes to extrathyroidal T3 production and maintenance of serum T3.

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Section: Discussionmentioning

confidence: 72%

Section: Discussionmentioning

confidence: 99%

Type 2 Iodothyronine Selenodeiodinase Is Expressed throughout the Mouse Skeleton and in the MC3T3-E1 Mouse Osteoblastic Cell Line during Differentiation

et al. 2005

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“…Previous work has shown that IL-6 augments 1,25(OH) 2 vitamin D 3 -induced OC differentiation from BM cells through IL-6R and gp130. 33,34 The results showing that C3 Ϫ/Ϫ or C3aR Ϫ/Ϫ C5aR Ϫ/Ϫ BM cells produce ϳ 5-fold less IL-6 during differentiation than WT BM cells ( Figure 6A) argue that IL-6 production by BM cells during OC differentiation is regulated by C3aR/C5aR. The results showing that supplementation of IL-6 into C3 Ϫ/Ϫ BM cells augmented TRAP-positive cell production ( Figure 6B), and that neutralization of IL-6 in WT or C3 Ϫ/Ϫ BM cells stimulated with C3a/C5a efficiently inhibited exogenous complement-induced OC differentiation ( Figure 6C-D), support the concept that IL-6 could play an important role in complementregulated OC differentiation.…”

Section: Discussionmentioning

confidence: 99%

Efficient osteoclast differentiation requires local complement activation

Dennis

et al. 2010

Blood

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Previous studies using blocking antibodies suggested that bone marrow (BM)-derived C3 is required for efficient osteoclast (OC) differentiation, and that C3 receptors are involved in this process. However, the detailed underlying mechanism and the possible involvement of other complement receptors remain unclear. In this report, we found that C3 ؊/؊ BM cells exhibited lower RANKL/OPG expression ratios, produced smaller amounts of macrophage colonystimulating factor and interleukin-6 (IL-6), and generated significantly fewer OCs than wild-type (WT) BM cells. During differentiation, in addition to C3, WT BM cells locally produced all other complement components required to activate C3 and to generate C3a/C5a through the alternative pathway, which is required for efficient OC differentiation. Abrogating C3aR/C5aR activity either genetically or pharmaceutically suppressed OC generation, while stimulating WT or C3 ؊/؊ BM cells with exogenous C3a and/or C5a augmented OC differentiation. Furthermore, supplementation with IL-6 rescued OC generation from C3 ؊/؊ BM cells, and neutralizing antibodies to IL-6 abolished the stimulatory effects of C3a/C5a on OC differentiation. These data indicate that during OC differentiation, BM cells locally produce components, which are activated through the alternative pathway to regulate OC differentiation. In addition to C3 receptors, C3aR/C5aR also regulate OC differentiation, at least in part, by modulating local IL-6 production. (Blood. 2010;116(22):4456-4463) IntroductionC3 is the central part of the complement system, which is pivotal in fighting infection and clearing out immune complexes as part of the innate immunity. For C3 to impact any cell, it needs to be activated through 1 of the 3 activating pathways: the classical, the alternative, or the lectin pathway. To form the C3 convertase (C3bBb) that is required in the alternative-pathway complement-activation cascade, C3b is generated from spontaneous C3 hydrolysis and binds to the active form of factor B (Bb), which is produced by the enzymatic activity of factor D. After the enzymatic activities of these C3/C5 convertases, the resultant complement-activation products bind to their receptors, facilitating cell migration, 1 phagocytosis, 2 as well as many other cellular activities. For cell surface-bound complement activation products, such as C3b and its derivatives, there are the C3 receptors, CR1, 3 CR2, 4 CR3, 5 and CR4 6 ; for the released complement-activation products, such as C3a and C5a, 1 there are C3aR 7 and C5aR. 8 C3aR and C5aR are G protein-coupled receptors that are present on a broad spectrum of cells. 9 C3a and C5a (also known as, anaphylatoxins) are small polypeptides, 10 which bind to C3aR and C5aR with high affinity (K d ϭ 1 nM) to modulate many cell activities, including stimulating the production of interleukin (IL)-6 (reviewed in Haas and van Strijp 11 ).In 1993, Dr Suda and his colleagues reported that the activated form of vitamin D, 1,25(OH) 2 vitamin D 3 , induces bone marrow (BM) cells to locally p...

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“…However, the precise events induced by IL-6 that mediate both these elements of bone remodeling are only partially understood. Although there is convincing evidence that IL-6 alone has no direct effect on osteoclast-like cells in vitro (46,47) or in vivo (48), neutralizing anti-IL-6 antibodies and anti-IL-6 receptor antibodies have been reported to inhibit the stimulatory effects of 1,25-dihydroxy vitamin D3 on osteoclastogenesis (47,49). Similarly, PTHinduced bone resorption in cocultures of osteoblasts and osteoclasts has been shown to be partially dependent upon IL-6 receptor activation (50).…”

Section: Discussionmentioning

confidence: 99%

Cross-Talk between the Interleukin-6 and Prostaglandin E2 Signaling Systems Results in Enhancement of Osteoclastogenesis through Effects on the Osteoprotegerin/Receptor Activator of Nuclear Factor-κB (RANK) Ligand/RANK System

et al. 2005

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The osteoprotegerin (OPG)/receptor activator of nuclear factor-kappaB ligand (RANKL)/receptor activator of nuclear factor-kappaB (RANK) system is the dominant and final mediator of osteoclastogenesis. Abnormalities of this system have been implicated in the pathogenesis of many skeletal diseases. Cyclooxygenase (COX)-2 and prostaglandin (PG)E(2), a major eicosanoid product of the COX-2-catalyzed pathway, play key roles in normal bone tissue remodeling. PGE(2) exerts its actions by binding and activating the E series of prostaglandin (EP) receptor. Activation of EP(2) and EP(4) receptors is associated with PGE(2)-induced osteoclast differentiation. IL-6, a major proinflammatory cytokine, has also been reported to induce osteoclast differentiation. Although interactions between the COX-2/PGE(2) and IL-6 systems have been described in bone cells, the mechanisms underlying these cooperative signaling pathways and the possible involvement of the OPG/RANKL/RANK system have not been fully elucidated. We demonstrate that COX-2, PGE(2), and IL-6 stimulate osteoblast growth and osteoclast differentiation. Effects on osteoclast differentiation, particularly with IL-6, were most marked when osteoclast precursor cells were grown in coculture with osteoblasts, indicating a possible role of the RANK/RANKL/OPG system. COX-2 and PGE(2) stimulated osteoclastogenesis through inhibition of OPG secretion, stimulation of RANKL production by osteoblasts, and up-regulation of RANK expression in osteoclasts. PGE(2) stimulated IL-6 secretion by bone cells, whereas COX-2 inhibitors decreased this same parameter. IL-6, in turn, increased PGE(2) secretion, COX-2, and EP receptor subtype expression in bone cells. Finally, IL-6 was the mediator of PGE(2)-induced suppression of OPG production by osteoblasts. These findings provide evidence for cross-talk between the PGE(2) and IL-6 signaling enhance osteoclast differentiation via effects on the OPG/RANKL/RANK system in bone cells.

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Interaction of Triiodothyronine With 1α,25-Dihydroxyvitamin D3 on Interleukin-6-Dependent Osteoclast-like Cell Formation in Mouse Bone Marrow Cell Cultures

Cited by 30 publications

References 26 publications

Type 2 Iodothyronine Selenodeiodinase Is Expressed throughout the Mouse Skeleton and in the MC3T3-E1 Mouse Osteoblastic Cell Line during Differentiation

Type 2 Iodothyronine Selenodeiodinase Is Expressed throughout the Mouse Skeleton and in the MC3T3-E1 Mouse Osteoblastic Cell Line during Differentiation

Efficient osteoclast differentiation requires local complement activation

Cross-Talk between the Interleukin-6 and Prostaglandin E2 Signaling Systems Results in Enhancement of Osteoclastogenesis through Effects on the Osteoprotegerin/Receptor Activator of Nuclear Factor-κB (RANK) Ligand/RANK System

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