A crucial role for thiol antioxidants in estrogen-deficiency bone loss

Lean, Jenny M.; Davies, Julie T.; Fuller, K.; Jagger, C. J.; Kirstein, Barrie; Partington, Geoffrey A.; Urry, Zoë; Chambers, T.J.

doi:10.1172/jci18859

Cited by 271 publications

(326 citation statements)

References 57 publications

Supporting

Mentioning

312

Contrasting

Unclassified

Order By: Relevance

“…Previous reports suggest that ROS, such as hydrogen peroxide and superoxide, enhance bone resorption 8,9 and that the partial depletion of glutathione brought on by treatment with a small amount of L-buthionine-(S,R)-sulfoximine (BSO, 10 mM), a specific inhibitor of g-GCS, stimulates RANKL-induced OC differentiation. 17 These results suggest that the severe depletion and adequate repletion of glutathione at the period of RANKL-induced glutathione reduction could have an effect on OC differentiation. It was thus speculated that a perturbation in redox status could result in mis-regulation of OC differentiation.…”

Section: Effects Of An Oxidizing or Reducing Cellular Redox Status Onmentioning

confidence: 80%

“…Bar, 25 mm OC formation and bone resorption. 8,9,11,17 Overexpression of catalase 10 and treatment with DPI, 11 a specific NADPH oxidase inhibitor, have indeed been shown to decrease superoxide production in OCs and block OC formation and bone resorption. In addition, it has been reported that a small amount of H 2 O 2 (1 mM) and a partial depletion of the intracellular glutathione pool by BSO (10 mM) enhance RANKL-induced OC differentiation via NF-kB activation.…”

Section: Inhibitory Effect Of Combined Rankl and Bso On Cell Growthmentioning

confidence: 99%

“…In addition, it has been reported that a small amount of H 2 O 2 (1 mM) and a partial depletion of the intracellular glutathione pool by BSO (10 mM) enhance RANKL-induced OC differentiation via NF-kB activation. 17 It is well known that ROS are linked with cellular signaling as second messengers. 23,24 Thus, transient elevation of endogenously generated ROS and an appropriate amount of exogenously treated ROS are essential to mediating signal transduction.…”

Section: Inhibitory Effect Of Combined Rankl and Bso On Cell Growthmentioning

confidence: 99%

See 2 more Smart Citations

Regulation of osteoclast differentiation by the redox-dependent modulation of nuclear import of transcription factors

Kim

et al. 2005

Cell Death Differ

View full text Add to dashboard Cite

This study sought to characterize the reduced glutathione (GSH)/oxidized GSSG ratio during osteoclast differentiation and determine whether changes in the intracellular redox status regulate its differentiation through a RANKL-dependent signaling pathway. A progressive decrease of the GSH/ GSSG ratio was observed during osteoclast differentiation, and the phenomenon was dependent on a decrease in total glutathione via downregulation of expression of the cglutamylcysteinyl synthetase modifier gene. Glutathione depletion by L-buthionine-(S,R)-sulfoximine (BSO) was found to inhibit osteoclastogenesis by blocking nuclear import of NF-jB and AP-1 in RANKL-propagated signaling and bone pit formation by increasing BSO concentrations in mature osteoclasts. Furthermore, intraperitoneal injection of BSO in mice resulted in an increase in bone density and a decrease of the number of osteoclasts in bone. Conversely, glutathione repletion with either N-acetylcysteine or GSH enhanced osteoclastogenesis. These findings indicate that redox status decreases during osteoclast differentiation and that this modification directly regulates RANKL-induced osteoclastogenesis.

show abstract

Section: Effects Of An Oxidizing or Reducing Cellular Redox Status Onmentioning

confidence: 80%

Section: Inhibitory Effect Of Combined Rankl and Bso On Cell Growthmentioning

confidence: 99%

Section: Inhibitory Effect Of Combined Rankl and Bso On Cell Growthmentioning

confidence: 99%

See 1 more Smart Citation

Regulation of osteoclast differentiation by the redox-dependent modulation of nuclear import of transcription factors

Kim

et al. 2005

Cell Death Differ

View full text Add to dashboard Cite

show abstract

Section: Supplemental Nac In Aging Humans and Rodents Provides Versatmentioning

confidence: 99%

“…The increase in osteolysis consequent to ovariectomy in rats is associated with a decline in bone marrow glutathione content (Lean et al 2003). Administration of NAC to rats prevented ovariectomy-induced bone loss-whereas administration of an agent that inhibits glutathione synthesis promoted bone loss in intact rats (Lean et al 2003). In a small, randomized, placebo-controlled clinical trial, 21 early postmenopausal patients were all placed on calcium/vitamin D supplementation, and in addition received 2 g NAC daily or matched placebo for 3 months (Sanders et al 2007).…”

Section: Supplemental Nac In Aging Humans and Rodents Provides Versatmentioning

confidence: 99%

An increased need for dietary cysteine in support of glutathione synthesis may underlie the increased risk for mortality associated with low protein intake in the elderly

McCarty

DiNicolantonio

2015

AGE

View full text Add to dashboard Cite

Restricted dietary intakes of protein or essential amino acids tend to slow aging and boost lifespan in rodents, presumably because they downregulate IGF-I/ Akt/mTORC1 signaling that acts as a pacesetter for aging and promotes cancer induction. A recent analysis of the National Health and Nutrition Examination Survey (NHANES) III cohort has revealed that relatively low protein intakes in mid-life (under 10 % of calories) are indeed associated with decreased subsequent risk for mortality. However, in those over 65 at baseline, such low protein intakes were associated with increased risk for mortality. This finding accords well with other epidemiology correlating relatively high protein intakes with lower risk for loss of lean mass and bone density in the elderly.

show abstract

Amorphous Silica: A New Antioxidant Role for Rapid Critical‐Sized Bone Defect Healing

Ilyas

Odatsu

Shah

et al. 2016

Adv Healthcare Materials

View full text Add to dashboard Cite

Traumatic fractures cause structurally unstable sites due to severe bone loss. Such fractures generate a high yield of reactive oxygen species (ROS) that can lead to oxidative stress. Excessive and prolonged ROS activity impedes osteoblast differentiation and instigates long healing times. Stimulation of antioxidants such as superoxide dismutase (SOD1), are crucial to reduce ROS, stimulate osteogenesis, and strengthen collagen and mineral formation. Yet, no current fixative devices have shown an ability to enhance collagen matrix formation through antioxidant expression. This study reports plasma-enhanced chemical vapor deposition based amorphous silicon oxynitride (Si(ON)x) as a potential new fracture healing biomaterial that adheres well to the implant surface, releases Si(+4) to enhance osteogenesis, and forms a surface hydroxyapatite for collagen mineral attachment. These materials provide a sustained release of Si(+4) in physiological environment for extended times. The dissolution rate partially depends on the film chemistry and can be controlled by varying O/N ratio. The presence of Si(+4) enhances SOD1, which stimulates other osteogenic markers downstream and leads to rapid mineral formation. In vivo testing using a rat critical-sized calvarial defect model shows a more rapid bone-regeneration for these biomaterials as compared to control groups, that implies the clinical significance of the presented biomaterial.

show abstract

A crucial role for thiol antioxidants in estrogen-deficiency bone loss

Cited by 271 publications

References 57 publications

Regulation of osteoclast differentiation by the redox-dependent modulation of nuclear import of transcription factors

Regulation of osteoclast differentiation by the redox-dependent modulation of nuclear import of transcription factors

An increased need for dietary cysteine in support of glutathione synthesis may underlie the increased risk for mortality associated with low protein intake in the elderly

Amorphous Silica: A New Antioxidant Role for Rapid Critical‐Sized Bone Defect Healing

Contact Info

Product

Resources

About