4-Phenylthiazole derivatives inhibit IL-6 secretion in osteoblastic cells and suppress bone weight loss in ovariectomized mice

Yamaguchi, Kohji; Yada, Mika; Tsuji, Tomoko; Hatanaka, Yasuo; Goda, Kenichi; Kobori, Takeo

doi:10.1016/s0960-894x(99)00122-5

Cited by 23 publications

(8 citation statements)

References 10 publications

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“…reported that the IL-6 secreted by osteosarcoma cells inhibits BMSC osteogenic differentiation [ 39 ]. Some drugs could suppress bone loss via the inhibition of IL-6 expression [ 40 – 44 ]. Our findings differ from those of Huh et al .…”

Section: Discussionmentioning

confidence: 99%

IL-6 Contributes to the Defective Osteogenesis of Bone Marrow Stromal Cells from the Vertebral Body of the Glucocorticoid-Induced Osteoporotic Mouse

Zhou

Zhang

et al. 2016

PLoS ONE

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Osteoporosis is one of the most prevalent skeletal system diseases. It is characterized by a decrease in bone mass and microarchitectural changes in bone tissue that lead to an attenuation of bone resistance and susceptibility to fracture. Vertebral fracture is by far the most prevalent osteoporotic fracture. In the musculoskeletal system, osteoblasts, originated from bone marrow stromal cells (BMSC), are responsible for osteoid synthesis and mineralization. In osteoporosis, BMSC osteogenic differentiation is defective. However, to date, what leads to the defective BMSC osteogenesis in osteoporosis remains an open question. In the current study, we made attempts to answer this question. A mouse model of glucocorticoid-induced osteoporosis (GIO) was established and BMSC were isolated from vertebral body. The impairment of osteogenesis was observed in BMSC of osteoporotic vertebral body. The expression profiles of thirty-six factors, which play important roles in bone metabolisms, were compared through antibody array between normal and osteoporotic BMSC. Significantly higher secretion level of IL-6 was observed in osteoporotic BMSCs compared with normal control. We provided evidences that IL-6 over-secretion impaired osteogenesis of osteoporotic BMSC. Further, it was observed that β-catenin activity was inhibited in response to IL-6 over-secretion. More importantly, in vivo administration of IL-6 neutralizing antibody was found to be helpful to rescue the osteoporotic phenotype of mouse vertebral body. Our study provides a deeper insight into the pathophysiology of osteoporosis and identifies IL-6 as a promising target for osteoporosis therapy.

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Section: Discussionmentioning

confidence: 99%

IL-6 Contributes to the Defective Osteogenesis of Bone Marrow Stromal Cells from the Vertebral Body of the Glucocorticoid-Induced Osteoporotic Mouse

Zhou

Zhang

et al. 2016

PLoS ONE

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“…These results led to the elucidation of the molecular events that govern this membrane-to-nucleus signalling pathway. More recent phenotype-based screens have yielded reagents that block mitotic progression 61,62,70 , induce or suppress cell-cycle arrest 11,66,71 , prevent mating-pheromone-induced cell-cycle arrest 23,72 , prevent interleukin-6 (IL-6) secretion 73 , induce apoptosis 74 and prevent endothelial cell activation 75 .…”

Section: Phenotype-based Screensmentioning

confidence: 99%

Chemical genetics: ligand-based discovery of gene function

2000

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Chemical genetics is the study of gene-product function in a cellular or organismal context using exogenous ligands. In this approach, small molecules that bind directly to proteins are used to alter protein function, enabling a kinetic analysis of the in vivo consequences of these changes. Recent advances have strongly enhanced the power of exogenous ligands such that they can resemble genetic mutations in terms of their general applicability and target specificity. The growing sophistication of this approach raises the possibility of its application to any biological process.

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“…, 2000), Sir2‐mediated transcriptional silencing in yeast (Grozinger et al. , 2001), membrane trafficking and secretion (Yamaguchi et al. , 1999; Feng et al.…”

Section: Small Molecules and Small Molecule Approachesmentioning

confidence: 99%

Using small molecules to study big questions in cellular microbiology

2002

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Summary High‐throughput screening of small molecules is used extensively in pharmaceutical settings for the purpose of drug discovery. In the case of antimicrobials, this involves the identification of small molecules that are significantly more toxic to the microbe than to the host. Only a small percentage of the small molecules identified in these screens have been studied in sufficient detail to explain the molecular basis of their antimicrobial effect. Rarer still are small molecule screens undertaken with the explicit goal of learning more about the biology of a particular microbe or the mechanism of its interaction with its host. Recent technological advances in small molecule synthesis and high‐throughput screening have made such mechanism‐directed small molecule approaches a powerful and accessible experimental option. In this article, we provide an overview of the methods and technical requirements and we dis‐cuss the potential of small molecule approaches to address important and often otherwise experimentally intractable problems in cellular microbiology.

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4-Phenylthiazole derivatives inhibit IL-6 secretion in osteoblastic cells and suppress bone weight loss in ovariectomized mice

Cited by 23 publications

References 10 publications

IL-6 Contributes to the Defective Osteogenesis of Bone Marrow Stromal Cells from the Vertebral Body of the Glucocorticoid-Induced Osteoporotic Mouse

IL-6 Contributes to the Defective Osteogenesis of Bone Marrow Stromal Cells from the Vertebral Body of the Glucocorticoid-Induced Osteoporotic Mouse

Chemical genetics: ligand-based discovery of gene function

Using small molecules to study big questions in cellular microbiology

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