Recent Insights into the Implication of Nitric Oxide in Osteoblast Differentiation and Proliferation during Bone Development

Saura, Marta; Tarin, Carlos; Zaragoza, Carlos

doi:10.1100/tsw.2010.58

Cited by 67 publications

(73 citation statements)

References 100 publications

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“…The role of NO in bone homeostasis has been confirmed [van't Hof and Ralston, 2001;Chow, 2000;Teixeira et al, 2008]. Mice lacking endothelial NO exhibit profound abnormalities in bone formation in the significant delay of osteoblast differentiation [Saura et al, 2010]. Moreover, there are indications that NO is a key molecule for the intra-and intercellular response to mechanical stimuli [Vatsa et al, 2007].…”

Section: Discussionmentioning

confidence: 96%

A Key Role of Autophagy in Osteoblast Differentiation on Titanium-Based Dental Implants

Kaluđerović

Mojić

Schreckenbach³

et al. 2014

Cells Tissues Organs

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Autophagy plays an important role in embryogenesis, for the maintenance of tissue homeostasis and the elimination of damaged subcellular structures. Furthermore, autophagy could be a mode of physiological cell death and also be implicated in cell differentiation. Thus, we hypothesized that autophagy may have an impact on the differentiation of osteoblast cells influenced by various titanium-based surfaces. Interactions between smooth, commercially available pure titanium (Ti cp), rough Ticer, acid-etched Ti cp (SS) and M1-M3 (comprised of the monoclinic phase of sodium-titanium oxides and rutile; M2 contains amorphous calcium phosphates) and human osteoblast cells were investigated. Immunofluorescent staining was used for detecting autophagy, cell cluster formation and collagen type I (Col-1) expression. Flow cytometry was employed to identify autophagy, the production of endogenous nitric oxide (NO) and the size and granularity of the cells. Rough surfaces caused osteoblast differentiation via the autophagic-dependent PI3/Akt signalling pathway. These surfaces induced the formation of discrete populations of large, granular cells, i.e. mature osteoblasts. In addition, M1-M3 provoked the development of a third population of small, granular cells, responsible for cell cluster formation, which are important for the formation of bone noduli and mineralisation. The same surfaces induced faster osteoblast maturation and enhanced NO production, a hallmark of the already mentioned processes. Neither the mature osteoblasts nor the small cells appeared after the inhibition of autophagy. Inhibition of autophagy also prevented cell cluster formation. We demonstrate that autophagy plays an essential role in the osteoblast differentiation on titanium-based surfaces with rough topography.

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Section: Discussionmentioning

confidence: 96%

A Key Role of Autophagy in Osteoblast Differentiation on Titanium-Based Dental Implants

Kaluđerović

Mojić

Schreckenbach³

et al. 2014

Cells Tissues Organs

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“…Inhibition of NO production in mice was shown to cause severe abnormalities in bone formation because of delaying osteoblast differentiation [87]. Some of the research pointed to a key role of NO in both intra-and intercellular response to mechanic stimuli [88].…”

Section: Discussionmentioning

confidence: 99%

Ti-SLActive and TiZr-SLActive Dental Implant Surfaces Promote Fast Osteoblast Differentiation

et al. 2017

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A primary goal in modern surface modification technology of dental implants is to achieve biocompatible surfaces with rapid but controlled healing which also allow health and longevity of implants. In order to realize all, understanding of osseointegration phenomena is crucial. Although Ti-SLA, Ti-SLActive and TiZr-SLActive surfaces have been successfully used in clinical implantology and were shown to notably reduce the primary healing time, available in vitro studies are sparse and do not concern or explore the mechanism(s) involved in human osteoblast behavior on these surfaces. Ti-SLA, Ti-SLActive, TiZr-SLActive, Ti cp, Ticer and Cercon surfaces were used. Osteoblast proliferation, cell cluster formation, morphological changes, induction of autophagy, nitric oxide (NO), reactive oxygen species/reactive nitrogen species (ROS/RNS) formation, osteocalcin (OC), bone sialoprotein (BSP) and collagen type I (Col-1) affected by various surfaces were analyzed. These surfaces induced formation of mature osteoblasts caused by elevated oxidative stress (ROS) followed by overexpression of osteoblast maturation key molecule (NO), with different intensity however. These mature osteoblasts induced upregulation of OC, BSP and Col-1, activating PI3/Akt signalling pathway resulting in autophagy, known as an important process in differentiation of osteoblast cells. Additional distinctive subpopulation identified on Ticer, Ti-SLA (after 5 days), Ti-SLActive and TiZr-SLActive surfaces (after 2 days) were forming cell clusters, essential for bone noduli formation and mineralisation. The results suggest that Ti-and TiZr-SLActive possess advanced properties in comparison with Ticer and Ti-SLA manifested as accelerated osteoblast differentiation. These effects could explain already known fast osseointegration of these surfaces in vivo.

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“…Activation of the iNOS system has been shown to partly mediate inflammationinduced osteoporosis [16] . High concentrations of NO, such as those observed after stimulation with pro-inflammatory cytokines, not only mediate cytokine-induced apoptosis [17] but also have potent inhibitory effects on osteoblast growth and differentiation [20,36,37] . Therefore, Sirt1 exerted its protective role against TNF-α, at least in part, through suppressing iNOS protein expression downstream of NF-κB.…”

Section: Discussionmentioning

confidence: 99%

Sirt1 overexpression protects murine osteoblasts against TNF-α-induced injury in vitro by suppressing the NF-κB signaling pathway

et al. 2012

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Aim: Sirtuin 1 (Sirt1) is the class III histone/protein deacetylase that interferes with the NF-κB signaling pathway, thereby has antiinflammatory function. This study was undertaken to investigate whether Sirt1 could protect osteoblasts against TNF-α-induced injury in vitro. Methods: Murine osteoblastic cell line, MC3T3-E1, was used. Overexpress of Sirt1 protein in MC3T3-E1 cells was made by transfection the cells with Sirt1-overexpressing adenovirus. The levels of mRNAs and proteins were determined with qRT-PCR and Western blotting, respectively. The activity of NF-κB was examined using NF-κB luciferase assay. The NO concentration was measured using the Griess method. Results: Treatment of MC3T3-E1 cells with TNF-α (2.5-10 ng/mL) suppressed Sirt1 protein expression in a concentration-dependent manner. TNF-α (5 ng/mL) resulted in an increase in apoptosis and a reduction in ALP activity in the cells. Overexpression of Sirt1 in the cells significantly attenuated TNF-α-induced injury through suppressing apoptosis, increasing ALP activity, and increasing the expression of Runx2 and osteocalcin mRNAs. Furthermore, overexpression of Sirt1 in the cells significantly suppressed TNF-α-induced NF-κB activation, followed by reducing the expression of iNOS and NO formation. Sirt1 activator resveratrol (10 µmol/L) mimicked the protection of the cells by Sirt1 overexpression against TNF-α-induced injury, which was reversed by the Sirt1 inhibitor EX-527 (5 µmol/L). Conclusion: Overexpression of Sirt1 protects MC3T3-E1 osteoblasts aganst TNF-α-induced cell injury in vitro, at least in part, via suppressing NF-κB signaling. Sirt1 may be a novel therapeutic target for treating rheumatoid arthritis-related bone loss.

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Recent Insights into the Implication of Nitric Oxide in Osteoblast Differentiation and Proliferation during Bone Development

Cited by 67 publications

References 100 publications

A Key Role of Autophagy in Osteoblast Differentiation on Titanium-Based Dental Implants

A Key Role of Autophagy in Osteoblast Differentiation on Titanium-Based Dental Implants

Ti-SLActive and TiZr-SLActive Dental Implant Surfaces Promote Fast Osteoblast Differentiation

Sirt1 overexpression protects murine osteoblasts against TNF-α-induced injury in vitro by suppressing the NF-κB signaling pathway

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