Osteoblast Apoptosis and Bone Turnover

Hock, Janet M.; Krishnan, Venkatesh; Onyia, Jude E.; Bidwell, Joseph P.; Milas, Jasminka; Stanislaus, Dinesh

doi:10.1359/jbmr.2001.16.6.975

Cited by 216 publications

(138 citation statements)

References 111 publications

(141 reference statements)

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“…In contrast to published reports indicating that pharmacological concentrations of glucocorticoids increase OB and OCY apoptosis [Manolagas, 2000;Hock et al, 2001;Boyce et al, 2002], treatment of HOB cells representing pre-OBs and mature-OBs with Dex downregulated sFRP-1 mRNA levels and inhibited PCD. Other studies have also reported that Dex treatment suppresses OB apoptosis in vitro [Zalavras et al, 2003].…”

Section: Discussioncontrasting

confidence: 85%

“…Finally, although estrogens and PTH have been reported to decrease OB and OCY apoptosis [Manolagas, 2000;Hock et al, 2001;Boyce et al, 2002], treatment of the HOB cells with these hormones did not affect sFRP-1 gene expression or cell viability.…”

Section: Discussionmentioning

confidence: 91%

“…Although we did not examine the effect of IL-1b on HOB cell viability, this too may correspond with an increase in apoptosis. Another boneresorbing cytokine with actions similar to IL-1b, TNF-a [McCarthy et al, 2000;Mundy et al, 2003], has also been reported to increase OB PCD in vitro [Hock et al, 2001], and both IL-1b and TNF-a activate nuclear factor (NF)-kb signaling [Baldwin, 1996]. On the other hand, treatment of pre-OBs and mature-OBs with vitamin D 3 suppressed sFRP-1 message levels.…”

Section: Discussionmentioning

confidence: 99%

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The Wnt antagonist secreted frizzled‐related protein‐1 controls osteoblast and osteocyte apoptosis

Bodine¹,

Billiard²,

Moran³

et al. 2005

J of Cellular Biochemistry

157

113

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Mechanisms controlling human bone formation remain to be fully elucidated. We have used differential display-polymerase chain reaction analysis to characterize osteogenic pathways in conditionally immortalized human osteoblasts (HOBs) representing distinct stages of differentiation. We identified 82 differentially expressed messages and found that the Wnt antagonist secreted frizzled-related protein (sFRP)-1 was the most highly regulated of these. Transient transfection of HOBs with sFRP-1 suppressed canonical Wnt signaling by 70% confirming its antagonistic function in these cells. Basal sFRP-1 mRNA levels increased 24-fold during HOB differentiation from pre-osteoblasts to pre-osteocytes, and then declined in mature osteocytes. This expression pattern correlated with levels of cellular viability such that the preosteocytes, which had the highest levels of sFRP-1 mRNA, also had the highest rate of cell death. Basal sFRP-1 mRNA levels also increased 29-fold when primary human mesenchymal stem cells were differentiated to osteoblasts supporting the developmental regulation of the gene. Expression of sFRP-1 mRNA was induced 38-fold following prostaglandin E 2 (PGE 2 ) treatment of pre-osteoblasts and mature osteoblasts that had low basal message levels. In contrast, sFRP-1 expression was down-regulated by as much as 80% following transforming growth factor (TGF)-b1 treatment of preosteocytes that had high basal mRNA levels. Consistent with this, treatment of pre-osteoblasts and mature osteoblasts with PGE 2 increased apoptosis threefold, while treatment of pre-osteocytes with TGF-b1 decreased cell death by 50%. Likewise, over-expression of sFRP-1 in HOBs accelerated the rate of cell death threefold. These results establish sFRP-1 as an important negative regulator of human osteoblast and osteocyte survival.

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Section: Discussioncontrasting

confidence: 85%

Section: Discussionmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

The Wnt antagonist secreted frizzled‐related protein‐1 controls osteoblast and osteocyte apoptosis

Bodine¹,

Billiard²,

Moran³

et al. 2005

J of Cellular Biochemistry

157

113

View full text Add to dashboard Cite

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“…(15) Many studies have provided evidence for TNF-a's apoptotic action in osteoblasts. (33)(34)(35) TNF-a also can augment apoptotic stimuli that are induced by Fas ligand or cycloheximide. (36) In osteoblastic cells, TNF-a's main apoptotic effects are mediated by tumor necrosis factor receptor 1 (TNFR1) and lead to the recruitment of TNFR1-associated death domain, which serves as a platform for generating various signaling complexes.…”

Section: Discussionmentioning

confidence: 99%

TNF-α's effects on proliferation and apoptosis in human mesenchymal stem cells depend on RUNX2 expression

Ghali

Chauveau

Hardouin

et al. 2010

Journal of Bone and Mineral Research

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RUNX2 is a bone-specific transcription factor that plays a critical role in prenatal bone formation and postnatal bone development. It regulates the expression of genes that are important in committing cells into the osteoblast lineage. There is increasing evidence that RUNX2 is involved in osteoblast proliferation. RUNX2 expression increases during osteoblast differentiation, and recent data even suggest that it acts as a proapoptotic factor. The cytokine tumor necrosis factor a (TNF-a) is known to modulate osteoblast functions in a manner that depends on the differentiation stage. TNF-a affects the rate at which mesenchymal precursor cells differentiate into osteoblasts and induces apoptosis in mature osteoblasts. Thus we sought to establish whether or not the effects of TNF-a and fetal calf serum on proliferation and apoptosis in human mesenchymal stem cells (hMSCs) were dependent on RUNX2 level and activity. We transfected hMSCs with small interfering RNAs (siRNAs) directed against RUNX2 and found that they proliferated more quickly than control hMSCs transfected with a nonspecific siRNA. This increase in proliferation was accompanied by a rise in cyclin A1, B1, and E1 expression and a decrease in levels of the cyclin inhibitor p21. Moreover, we observed that RUNX2 silencing protected hMSCs from TNF-a's antiproliferative and apoptotic effects. This protection was accompanied by the inhibition of caspase-3 activity and Bax expression. Our results confirmed that RUNX2 is a critical link between cell fate, proliferation, and growth control. This study also suggested that, depending on the osteoblasts' differentiation stage, RUNX2 may control cell growth by regulating the expression of elements involved in hormone and cytokine sensitivity. ß

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“…1 A balance among proliferation, differentiation, and apoptosis determines the population size of osteoblasts in the skeleton. 2 A variety of systemic and local factors are involved in the regulation of osteoblast activities. 3 Nitric oxide (NO), synthesized from L-arginine by NO synthases, has been shown to be one such factor.…”

Section: Introductionmentioning

confidence: 99%

Nitric oxide protects osteoblasts from oxidative stress‐induced apoptotic insults via a mitochondria‐dependent mechanism

Chang

Liao

Lin

et al. 2006

Journal Orthopaedic Research

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Nitric oxide (NO) contributes to the regulation of osteoblast activities. In this study, we evaluated the protective effects of NO pretreatment on oxidative stress-induced osteoblast apoptosis and its possible mechanism using neonatal rat calvarial osteoblasts as the experimental model. Exposure of osteoblasts to sodium nitroprusside (SNP) at a low concentration of 0.3 mM significantly increased cellular NO levels without affecting cell viability. However, when the concentration reached a high concentration of 2 mM, SNP increased the levels of intracellular reactive oxygen species and induced osteoblast injuries. Thus, administration of 0.3 and 2 mM SNP in osteoblasts were respectively used as sources of NO and oxidative stress. Pretreatment with NO for 24 h significantly ameliorated the oxidative stress-caused morphological alterations and decreases in alkaline phosphatase activity, and reduced cell death. Oxidative stress induced osteoblast death via an apoptotic mechanism, but NO pretreatment protected osteoblasts against the toxic effects. The mitochondrial membrane potential was significantly reduced following exposure to the oxidative stress. However, pretreatment with NO significantly lowered the suppressive effects. Oxidative stress increased cellular Bax protein production and cytochrome c release from mitochondria. Pretreatment with NO significantly decreased oxidative stress-caused augmentation of Bax and cytochrome c protein levels. In parallel with cytochrome c release, oxidative stress induced caspase-3 activation and DNA fragmentation. Pretreatment with NO significantly reduced the oxidative stress-enhanced caspase-3 activation and DNA damage. Results of this study show that NO pretreatment can protect osteoblasts from oxidative stress-induced apoptotic insults. The protective action involves a mitochondria-dependent mechanism. ß

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Osteoblast Apoptosis and Bone Turnover

Cited by 216 publications

References 111 publications

The Wnt antagonist secreted frizzled‐related protein‐1 controls osteoblast and osteocyte apoptosis

The Wnt antagonist secreted frizzled‐related protein‐1 controls osteoblast and osteocyte apoptosis

TNF-α's effects on proliferation and apoptosis in human mesenchymal stem cells depend on RUNX2 expression

Nitric oxide protects osteoblasts from oxidative stress‐induced apoptotic insults via a mitochondria‐dependent mechanism

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