Involvement of receptor activator of NFκB ligand and tumor necrosis factor-α in bone destruction in rheumatoid arthritis

Romas, E.; Gillespie, M. T.; Martın, Thomas

doi:10.1016/s8756-3282(01)00682-2

Cited by 384 publications

(300 citation statements)

References 76 publications

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“…Since the RANKL/RANK/ OPG system has been shown to be important in inflammation-induced bone resorption, including that in rheumatoid arthritis (27)(28)(29)46) and in periodontal disease (4,31), we focused on these molecules. Since RANKL mRNA expression in the MG-63 cells was scarce, we used neonatal mouse calvarial bones for these experiments, the rationale being that activation of BK receptors synergistically potentiates IL-1-induced bone resorption in the calvarial bones (11).…”

Section: Discussionmentioning

confidence: 99%

“…Mice deficient in OPG exhibit abundant osteoclasts and an osteoporotic phenotype. RANKL is expressed in synovial tissue from patients with rheumatoid arthritis (27)(28)(29) and has been found to be crucial for osteoclast formation and bone loss in experimentally induced arthritis in mice (30). RANKL is also expressed in gingival tissue from patients with periodontal disease (31,32), and increased RANKL/OPG is associated with bone loss in periodontitis (4,31).…”

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confidence: 99%

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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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Section: Discussionmentioning

confidence: 99%

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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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“…Treatment with TNF␣ is known to induce IL-1␤ production (34), and therefore we focused our investigation on the signaling cascades modulated by the IL-1 receptor (IL-1R). In SW-1353 cells, 4 main IL-1R signaling cascades have been linked to induction of MMP expression: NF-B and the MAPK pathways p38, JNK, and ERK (20).…”

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confidence: 99%

Regulation of matrix metalloproteinase gene expression by a retinoid X receptor–specific ligand

Burrage¹,

Huntington²,

Sporn³

et al. 2007

Arthritis & Rheumatism

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Objective. To evaluate the effects of LG100268 (LG268), a synthetic ligand for the nuclear hormone receptor retinoid X receptor, on the expression of matrix metalloproteinase 1 (MMP-1) and MMP-13 induced by proinflammatory cytokines in a chondrocyte model.Methods. SW-1353 human chondrosarcoma cells were used to study the effects of LG268 on interleukin-1␤ (IL-1␤)-stimulated MMP production and collagen degradation. Gene expression was determined by quantitative real-time reverse transcriptionpolymerase chain reaction, and protein levels were determined by Western blot analysis. Collagen degradation was determined by an in vitro matrix destruction assay. The effects of LG268 on nuclear protein binding and histone acetylation were determined by electrophoretic mobility shift assay and chromatin immunoprecipitation assay, respectively.Results.LG268 treatment specifically antagonized the IL-1␤-mediated induction of MMP-1 and MMP-13 heterogeneous nuclear RNA, messenger RNA, and protein. The inhibitory effect of LG268 was found to be due to a decrease in the rate of MMP-1 and MMP-13 transcription.LG268 treatment also prevented the in vitro degradation of a type I collagen matrix by IL-1␤-treated SW-1353 cells. The inhibitory effect of LG268 on MMP-1 and MMP-13 transcription appears to be mediated, at least in part, through modulation of histone modification in regions of the MMP-1 and MMP-13 promoters that contain binding sites for activator protein 1 transcription factors.Conclusion. These data indicate that LG268 treatment selectively inhibits inflammatory cytokineinduced production of MMP-1 and MMP-13 at the level of gene transcription and blocks collagen destruction by proinflammatory cytokine-stimulated chondrocytic cells. This study is among the first to describe how rexinoids affect gene expression, and the findings suggest that the rexinoid class of compounds may have a future role in preventing the irreversible collagen destruction seen in the arthritides.The destruction of joint tissues that is a hallmark of rheumatoid arthritis (RA) and osteoarthritis (OA) is mediated largely by members of the matrix metalloproteinase (MMP) family of enzymes (1-3). At low expression levels, these zinc-dependent endopeptidases maintain connective tissue homeostasis in a wide range of biologic functions (4). However, abnormally high levels of MMP expression have been linked to multiple pathologic states, including tumor invasion, atherosclerosis, and the arthritides (4). In humans, the MMP family currently encompasses 23 unique members, which degrade all constituents of the extracellular matrix (ECM) (5). The MMPs can be subdivided into 6 main classes (1,4,5), consisting of the collagenases (MMPs 1, 8, and 13), the gelatinases (MMPs 2 and 9), the stromelysins (MMPs 3, 10, and 11), the matrilysins (MMPs 7 and 26), the membrane-type MMPs (MMPs 14,15,16,17,24,and 25), and a diverse subgroup.The collagenase subgroup is unique in its ability to cleave fibrillar collagens, and their enzymatic activity represents a rate-limiting step...

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“…4 Receptor activator nuclear factor k B ligand (RANKL), believed to be the most important cytokine for normal osteoclastogenesis, is also involved in inflammatory bone resorption. 6 In addition to cytokines being involved in osteoclastogenesis, an involvement of factors bearing the ability of chemotaxis against cells in the osteoclast lineage should be considered.…”

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confidence: 99%

Possible involvement of MIP-1α in the recruitment of osteoclast progenitors to the distal tibia in rats with adjuvant-induced arthritis

Toh

Kukita

et al. 2004

Laboratory Investigation

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In the rat model of rheumatoid arthritis, a marked formation of osteoclasts is found in the distal tibia and the metatarsal bone. It was therefore postulated that osteoclast progenitors would be increased in the bone marrow cavities of rats with adjuvant-induced arthritis (AA rats). Bone marrow cells obtained from tibia of AA rats were cultured to form cells in the osteoclast lineage to access the number of osteoclast progenitors. Unexpectedly, only a suppressed level of osteoclast progenitors was detected in the diaphyseal bone marrow of tibia in AA rats. Distribution of osteoclast progenitors in the bone marrow cavity was examined, and it was shown that osteoclast progenitors accumulated in the distal tibia. Macrophage inflammatory protein (MIP)-1a, an osteoclastogenic CC chemokine, was expressed in ED-1-positive macrophages localizing in the distal tibia with marked bone destruction. Chemotaxis studies showed that MIP-1a expressed significant activity towards bone marrow cells. The suppressed level of osteoclastogenesis in bone marrow cells of AA rats was restored to a normal level by the addition of MIP-1a. It was suggested that MIP-1a is involved in the migration of osteoclast progenitors to the distal tibia as well as in osteoclastogenesis in AA rats. In these rats, in situ hybridization of the distal tibia with a high level of bone destruction showed significant expression of Receptor activator nuclear factor jB ligand (RANKL) messenger RNA in aggregates of multinucleated osteoclast-like cells present in the bone marrow cavity, a unique pathological feature for these rats. Migrated osteoclast progenitors are thought to be efficiently differentiated into osteoclasts in response to RANKL expressed by the aggregates of osteoclastlike cells under the influence of the MIP-1a. Such positive-feedback regulation of osteoclastogenesis could result in the highest recruitment of active osteoclasts in the area of marked bone destruction.

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Involvement of receptor activator of NFκB ligand and tumor necrosis factor-α in bone destruction in rheumatoid arthritis

Cited by 384 publications

References 76 publications

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

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

Regulation of matrix metalloproteinase gene expression by a retinoid X receptor–specific ligand

Possible involvement of MIP-1α in the recruitment of osteoclast progenitors to the distal tibia in rats with adjuvant-induced arthritis

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