Involvement of nitric oxide and biopterin in proinflammatory cytokine-induced apoptotic cell death in mouse osteoblastic cell line MC3T3-E1

Mogi, Makio; Kinpara, Kyoko; Kondo, Ayami; Togari, Akifumi

doi:10.1016/s0006-2952(99)00131-8

Cited by 39 publications

(32 citation statements)

References 23 publications

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“…Suppression of osteoblast viability or proliferation would interfere with the dynamic balance of bone remodeling, and lead to pathophysiological conditions of bone tissues [9]. Previous studies reveal that NO, over-induced by proinflammatory cytokines, has a pathogenic role when it acts as a mediator of these cytokines for the stimulation of osteoblast death [22,27]. This study shows that NO released by an extracellular NO donor also has the similar cytotoxic effects on osteoblasts as intracellular NO induction.…”

Section: Discussionmentioning

confidence: 60%

“…NO is a high energy radical and has the ability to cause DNA fragmentation by direct attack or indirect activation of serious signal transduction [3,37]. Previous studies have reported that NO induced by proinflammatory cytokines, tumor necrosis factor-ell, interleukin-1p and interferon-y, or an NO donor, Snitroso-N-acetyl-D,L-penicillamine would lead to DNA fragmentation and cell death of a mouse clonal osteogenic cell line, MC3T3-El cell [11,27]. The present study, using the primary culture system of normal rat calvarial osteoblasts, has shown that administration of the bone cells with SNP causes nuclear DNA fragmentation by the analyses of apoptotic cells and the DNA ladder.…”

Section: Controlmentioning

confidence: 99%

“…In an animal model of inflammation-induced osteoporosis, NO is induced and associated with the reduction of osteoblast numbers, the increase of osteoclast numbers, and the decrease of bone mineral density [l]. The induction of NO in osteoblasts following treatment with proinflammatory cytokines promotes cell death [11,27]. However, the death mechanism induced by NO is still little known.…”

Section: Introductionmentioning

confidence: 99%

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Nitric oxide induces osteoblast apoptosis through the de novo synthesis of Bax protein

Chen

Liu

Lin

et al. 2002

Journal Orthopaedic Research

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Nitric oxide (NO) plays a crucial role in the physiological and pathophysiological regulations of osteoblast functions. This study is designed to evaluate the toxic effects of NO released by sodium nitroprusside (SNP), an NO donor, on neonatal Wistar rat calvarial osteoblasts from the analyses of cell viability, alkaline phosphatase (ALP) activity, cell morphology, apoptotic cells, terminal deoxynucleotidyl transferase-mediated dUTP nick end-label (TUNEL) assay, DNA ladder, and immunocytochemistry and Western blot for proapoptotic Bax protein. SNP increased the levels of nitrite, an oxidative product of NO, in the culture medium of osteoblasts in concentration-and time-dependent manners, and altered cell morphologies to round and shrinkage shapes. Administration of osteoblasts with SNP resulted in concentration-and time-dependent decreases of cell viability and ALP activity. Analysis of apoptotic cells revealed that SNP increased the percentages of osteoblasts processing apoptosis. Analyses of TUNEL and DNA ladder showed that SNP caused DNA fragmentation. Pretreatment with cycloheximide, an inhibitor of protein synthesis, partially blocked SNP-induced osteoblast apoptosis. Imunocytochemical and immunoblotting analyses revealed that SN P increased Bax protein in osteoblasts. This study suggests that SNP could increase the levels of NO in osteoblasts, and cause osteoblast

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Section: Discussionmentioning

confidence: 60%

Section: Controlmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Nitric oxide induces osteoblast apoptosis through the de novo synthesis of Bax protein

Chen

Liu

Lin

et al. 2002

Journal Orthopaedic Research

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“…These results are in concordance with our observations and the conclusions of other investigations relating the immunoregulatory properties of IFN-␥. 1,10,16,18 Ukai et al 24 investigated the balance between IFN-␥ and IL-4-bearing cells in human inflamed gingiva by immunohistochemistry. A low ratio of IL-4-bearing cells to IFN-␥-bearing cells was involved in the destruction of periodontal tissue.…”

Section: Discussionmentioning

confidence: 99%

“…12,[16][17][18][19] Previous studies revealed that IFN-␥ inhibits bone resorption stimulated by interleukin (IL)-1 and blocks collagenase production caused by parathyroid hormone, prostaglandin E2, 1.25(OH)2 vitamin D3, IL-1, tumor necrosis factor-␣ (TNF-␣), and epidermal growth factor. [20][21][22] On the other hand, various investigations have introduced conflicting results suggesting that IFN-␥ modulates the function and activities of osteoblasts, osteoclasts, and chondrocytes, resulting in bone resorption, leukocyte function, and in defects of bone and cartilage.…”

Section: Introductionmentioning

confidence: 99%

Effects of Interferon-Gamma on Bone Remodeling during Experimental Tooth Movement

Mermut

Bengi

Akın

et al. 2007

The Angle Orthodontist

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Caspase‐2 deficiency protects mice from diabetes‐induced marrow adiposity

Coe

Lippner

Perez

et al. 2011

J of Cellular Biochemistry

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Type I (T1) diabetes is an autoimmune and metabolic disease associated with bone loss. Bone formation and density are decreased in T1-diabetic mice. Correspondingly, the number of TUNEL positive, dying osteoblasts increases in bones of T1-diabetic mice. Moreover, two known mediators of osteoblast death, TNFα and ROS, are increased in T1-diabetic bone. TNFα and oxidative stress are known to activate caspase-2, a factor involved in the extrinsic apoptotic pathway. Therefore, we investigated the requirement of caspase-2 for diabetes-induced osteoblast death and bone loss. Diabetes was induced in 16-week old C57BL/6 caspase-2 deficient mice and their wild type littermates and markers of osteoblast death, bone formation and resorption, and marrow adiposity were examined. Despite its involvement in extrinsic cell death, deficiency of caspase-2 did not prevent or reduce diabetes-induced osteoblast death as evidenced by a twofold increase in TUNEL positive osteoblasts in both mouse genotypes. Similarly, deficiency of caspase-2 did not prevent T1-diabetes induced bone loss in trabecular bone (BV/TV decreased by 30 and 50%, respectively) and cortical bone (decreased cortical thickness and area with increased marrow area). Interestingly, at this age, differences in bone parameters were not seen between genotypes. However, caspase-2 deficiency attenuated diabetes-induced bone marrow adiposity and adipocyte gene expression. Taken together, our data suggest that caspase-2 deficiency may play a role in promoting marrow adiposity under stress or disease conditions, but it is not required for T1-diabetes induced bone loss.

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Involvement of nitric oxide and biopterin in proinflammatory cytokine-induced apoptotic cell death in mouse osteoblastic cell line MC3T3-E1

Cited by 39 publications

References 23 publications

Nitric oxide induces osteoblast apoptosis through the de novo synthesis of Bax protein

Nitric oxide induces osteoblast apoptosis through the de novo synthesis of Bax protein

Effects of Interferon-Gamma on Bone Remodeling during Experimental Tooth Movement

Caspase‐2 deficiency protects mice from diabetes‐induced marrow adiposity

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