Sodium hydrosulfide inhibits the differentiation of osteoclast progenitor cells via NRF2-dependent mechanism

Gambari, Laura; Lisignoli, Gina; Cattini, Luca; Manferdini, Cristina; Facchini, Andrea; Grassi, Francesco

doi:10.1016/j.phrs.2014.06.014

Cited by 70 publications

(63 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recently L. Gambari et al have shown that sodium hydrosulphide (NaHS) a common H 2 S donor dose dependently decreased the osteoclast formation by upregulating the Nrf2 protein expression and its nuclear translocation. Furthermore, Nrf2 silencing in human pre osteoclasts completely abolished NaHS mediated inhibition of osteoclastogenesis which further strengthens the implication of ROS in osteoclast activation [38]. Antioxidant treatments have been proved to be effective to rescue the bone loss induced by oxidative stress by decreasing the NF-KB activation in osteoclasts and RANKL expression in osteoblasts.…”

Section: Discussionsupporting

confidence: 53%

Thymoquinone prevents RANKL-induced osteoclastogenesis activation and osteolysis in an in vivo model of inflammation by suppressing NF-KB and MAPK Signalling

Thummuri

Jeengar

Shrivastava

et al. 2015

Pharmacological Research

109

View full text Add to dashboard Cite

Section: Discussionsupporting

confidence: 53%

Thymoquinone prevents RANKL-induced osteoclastogenesis activation and osteolysis in an in vivo model of inflammation by suppressing NF-KB and MAPK Signalling

Thummuri

Jeengar

Shrivastava

et al. 2015

Pharmacological Research

109

View full text Add to dashboard Cite

“…H2S is a metabolic production of homocysteine by transsulfuration dependent on CBS, CSE, or MPST combined with cysteine aminotransferase (37). Recent studies highlight that H2S plays an essential role in osteoclast differentiation (11,23) and bone marrow MSC osteogenesis (26). In this study, we identified that osteoblasts predominantly expressed the CSE-H2S system, which sulfhydrated RUNX2 at C122 and C132 sites to increase RUNX2 activity, thereby enhancing osteoblast biologic function to promote bone fracture healing.…”

Section: Discussionmentioning

confidence: 77%

“…Recent studies reported that H2S promotes bone fracture healing in rabbit (15) and attenuates bone loss induced by estrogen deficiency (12); however, the mechanism is unclear. H2S decreases osteoclast differentiation induced by nicotine or lipopolysaccharide (23) and osteoclast progenitor differentiation (11), which decreases necrotic bone absorption during bone healing, but benefits osteoporosis. As well, H2S decreases matrix metalloproteinase activity in bone matrix (34), thereby accelerating matrix mineralization.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Cystathionine γ-Lyase–Hydrogen Sulfide Induces Runt-Related Transcription Factor 2 Sulfhydration, Thereby Increasing Osteoblast Activity to Promote Bone Fracture Healing

Zheng

Liao

Lin

et al. 2017

Antioxidants & Redox Signaling

View full text Add to dashboard Cite

Aims: Hydrogen sulfide (H2S) plays an essential role in bone formation, in part, by inhibiting osteoclast differentiation, maintaining mesenchymal stem cell osteogenesis ability, or reducing osteoblast injury. We aimed to investigate the role of H2S in osteoblast function and its possible molecular target. Results: In this study, we found that cystathionine c-lyase (CSE) majorly contributed to endogenous H2S production in the primary osteoblast. Overexpressed CSE increased osteoblast differentiation and maturation with higher bone morphogenetic protein 2 and osteopontin expression, alkaline phosphatase activity, and calcium nodule formation; in contrast, knockdown of CSE had opposite effects. Runt-related transcript factor 2 (RUNX2) is required for osteoblast biologic function. CSE-H2S increased nuclear RUNX2 accumulation, DNA binding activity, and target gene transcription. Protein sulfhydration is a common signal by H2S. We confirmed that RUNX2 was also sulfhydrated by H2S. This chemical modification enhanced RUNX2 transactivation, which was blocked by dithiothreitol (DTT, sulfhydration remover). Mutation of two cysteine sites in the runt domain of RUNX2 abolished H2S-induced RUNX2 sulfhydration and transactivation. In a bone -fracture rat model, overexpressed CSE promoted bone healing, which confirmed the effect of CSE-H2S on osteoblasts. Innovation: CSE-H2S is a dominant H2S generation system in osteoblasts and promotes osteoblast activity by the RUNX2 pathway, with RUNX2 sulfhydration as a novel transactivation regulation. Conclusion: CSE-H2S sulfhydrated RUNX2 enhanced its transactivation and increased osteoblast differentiation and maturation, thereby promoting bone healing. Antioxid. Redox Signal. 27, 742-753.

show abstract

“…Furthermore, SFN was shown to activate the transcription factor NRF2 (Nfe2l2), which promotes the expression of the two key antioxidant genes peroxiredoxin-1 and NAD(P)H dehydrogenase quinone 1, thus activating a sustained antioxidant response in osteoclast progenitors. The inhibition of osteoclast differentiation might thus also be associated with a down-regulation in RANKL-dependent intracellular reactive oxygen species levels in preosteoclastic cells (50). Thus, the effects observed by SFN in osteoclasts and in osteoblasts might also partially be attributed to its antioxidative proprieties.…”

Section: Discussionmentioning

confidence: 99%

Anabolic and Antiresorptive Modulation of Bone Homeostasis by the Epigenetic Modulator Sulforaphane, a Naturally Occurring Isothiocyanate

Thaler

Maurizi

Roschger

et al. 2016

Journal of Biological Chemistry

View full text Add to dashboard Cite

Bone degenerative pathologies like osteoporosis may be initiated by age-related shifts in anabolic and catabolic responses that control bone homeostasis. Here we show that sulforaphane (SFN), a naturally occurring isothiocyanate, promotes osteoblast differentiation by epigenetic mechanisms. SFN enhances active DNA demethylation via Tet1 and Tet2 and promotes preosteoblast differentiation by enhancing extracellular matrix mineralization and the expression of osteoblastic markers (Runx2, Col1a1, Bglap2, Sp7, Atf4, and Alpl). SFN decreases the expression of the osteoclast activator receptor activator of nuclear factor-B ligand (RANKL) in osteocytes and mouse calvarial explants and preferentially induces apoptosis in preosteoclastic cells via up-regulation of the Tet1/Fas/Caspase 8 and Caspase 3/7 pathway. These mechanistic effects correlate with higher bone volume (ϳ20%) in both normal and ovariectomized mice treated with SFN for 5 weeks compared with untreated mice as determined by microcomputed tomography. This effect is due to a higher trabecular number in these mice. Importantly, no shifts in mineral density distribution are observed upon SFN treatment as measured by quantitative backscattered electron imaging. Our data indicate that the food-derived compound SFN epigenetically stimulates osteoblast activity and diminishes osteoclast bone resorption, shifting the balance of bone homeostasis and favoring bone acquisition and/or mitigation of bone resorption in vivo. Thus, SFN is a member of a new class of epigenetic compounds that could be considered for novel strategies to counteract osteoporosis.

show abstract

Sodium hydrosulfide inhibits the differentiation of osteoclast progenitor cells via NRF2-dependent mechanism

Cited by 70 publications

References 54 publications

Thymoquinone prevents RANKL-induced osteoclastogenesis activation and osteolysis in an in vivo model of inflammation by suppressing NF-KB and MAPK Signalling

Thymoquinone prevents RANKL-induced osteoclastogenesis activation and osteolysis in an in vivo model of inflammation by suppressing NF-KB and MAPK Signalling

Cystathionine γ-Lyase–Hydrogen Sulfide Induces Runt-Related Transcription Factor 2 Sulfhydration, Thereby Increasing Osteoblast Activity to Promote Bone Fracture Healing

Anabolic and Antiresorptive Modulation of Bone Homeostasis by the Epigenetic Modulator Sulforaphane, a Naturally Occurring Isothiocyanate

Contact Info

Product

Resources

About