Necessity of inositol (1,4,5)-trisphosphate receptor 1 and μ-calpain in NO-induced osteoclast motility

Yaroslavskiy, Beatrice B.; Sharrow, Allison C.; Wells, Alan; Robinson, Lisa J.; Blair, Harry C.

doi:10.1242/jcs.004184

Cited by 28 publications

(43 citation statements)

References 53 publications

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“…These include, in addition to TNFα itself, TSG-6, a hyaluronan-binding protein that is a TNF-responsive product that activates bone resorption and decreases bone formation [20]. There were smaller but significant and consistent ~40% negative changes in several attachment and cytoskeletal regulating proteins, the Inositol-(1,4,5)-trisphosphate receptor-1 [17], cofilin, fibronectin, and the urokinase receptor PLAUR (Fig 4, right four bars). There were moderate and less consistent effects, mainly negative and in the ~20–30% range, on selected steroid response genes and chaperone proteins, such as HSP70.…”

Section: Resultsmentioning

confidence: 99%

“…Antibodies to the FSH receptor were rabbit anti-FSH receptor polyclonal AB75200 from AbCam (Cambridge, MA), recognizing an internal peptide of the extracellular domain of human FSH-R, or goat anti FSH-R polyclonal antibody sc7798, from Santa Cruz (Santa Cruz, CA, USA), raised against a 20 amino acid peptide from the N-terminal of human FSH-R. For Western blots, cells were lysed in 0.3% SDS, 50 mM tris, pH 7, with proteinase and phosphatase inhibitors [17]. Proteins were separated on SDS-PAGE, transferred to derivitized nylon, reacted with primary antibodies followed by alkaline phosphatase-coupled secondary antibodies and visualized by chemiluminescence (ECL plus, Amersham, Piscataway, NJ).…”

Section: Methodsmentioning

confidence: 99%

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FSH-receptor isoforms and FSH-dependent gene transcription in human monocytes and osteoclasts

Robinson

Tourkova

Wang

et al. 2010

Biochemical and Biophysical Research Communications

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121

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Cells of the monocyte series respond to follicle stimulating hormone (FSH) by poorly characterized mechanisms. We studied FSH-receptors (FSH-R) and FSH response in nontransformed human monocytes and in osteoclasts differentiated from these cells. Western blot and PCR confirmed FSH-R expression on monocytes or osteoclasts, although at low levels relative to ovarian controls. Monocyte and osteoclast FSH-Rs differed from FSH-R from ovarian cells, reflecting variable splicing in exons 8–10. Monocytes produced no cAMP, the major signal in ovarian cells, in response to FSH. However, monocytes or osteoclasts transcribed TNFα in response to the FSH. No relation of expression of osteoclast FSH-R to the sex of cell donors or to exposure to sex hormones was apparent. Controls for FSH purity and endotoxin contamination were negative. Unamplified cRNA screening in adherent CD14 cells after 2 hours in 25 ng/ml FSH showed increased transcription of RANKL signalling proteins. Transcription of key proteins that stimulate bone turnover, TNFα and TSG-6, increased 2–3 fold after FSH treatment. Smaller but significant changes occurred in transcripts of selected signalling, adhesion, and cytoskeletal proteins. We conclude that monocyte and osteoclast FSH response diverges from that of ovarian cells, reflecting, at least in part, varying FSH-R isoforms.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

FSH-receptor isoforms and FSH-dependent gene transcription in human monocytes and osteoclasts

Robinson

Tourkova

Wang

et al. 2010

Biochemical and Biophysical Research Communications

Self Cite

121

120

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“…Human monocytic osteoclast precursors were isolated by anti-CD14 immuno-magnetic selection from human blood buffy coat cells after density gradient centrifugation [29] and maintained in culture in Dulbecco’s Modified Eagle’s Medium (DMEM, Mediatech, Herndon, VA) with 10% fetal bovine serum (Hyclone, Logan, UT), penicillin (100 units/ml)/streptomycin (100 μg/ml) (Invitrogen, Carlsbad, CA) and 10 ng/ml of CSF-1 (R&D, Minneapolis, MN). Use of human cells was approved by the institutional review board.…”

Section: Methodsmentioning

confidence: 99%

Estrogen inhibits RANKL-stimulated osteoclastic differentiation of human monocytes through estrogen and RANKL-regulated interaction of estrogen receptor-α with BCAR1 and Traf6

Robinson

Yaroslavskiy

Griswold

et al. 2009

Experimental Cell Research

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The effects of estrogen on osteoclast survival and differentiation were studied using CD14-selected mononuclear osteoclast precursors from peripheral blood. Estradiol at ~1 nM reduced RANKLdependent osteoclast differentiation by 40-50%. Osteoclast differentiation was suppressed 14 days after addition of RANKL even when estradiol was withdrawn after 18 hours. In CD14+ cells apoptosis was rare and was not augmented by RANKL or by 17-β-estradiol. Estrogen receptor-α (ERα) expression was strongly down-regulated by RANKL, whether or not estradiol was present. Mature human osteoclasts thus cannot respond to estrogen via ERα. However, ERα was present in CD14+ osteoclast progenitors, and a scaffolding protein, BCAR1, which binds ERα in the presence of estrogen, was abundant. Immunoprecipitation showed rapid (~5 minute) estrogen-dependent formation of ERα-BCAR1 complexes, which were increased by RANKL co-treatment. The RANKLsignaling intermediate Traf6, which regulates NF-κB activity, precipitated with this complex. Reduction of NF-κB nuclear localization occurred within 30 minutes of RANKL stimulation, and estradiol inhibited the phosphorylation of IκB in response to RANKL. Inhibition by estradiol was abolished by siRNA knockdown of BCAR1. We conclude that estrogen directly, but only partially, curtails human osteoclast formation. This effect requires BCAR1 and involves a non-genomic interaction with ERα. KeywordsEstrogen receptor-α; Breast cancer antiestrogen resistance-1; p130Cas; Nuclear factor-κB; TNFreceptor associated factorsOsteoclasts are multinucleated bone-degrading cells that differentiate from monocytic precursors. They are critical to bone modeling and maintenance, and mediate the release of skeletal mineral for calcium and pH homeostasis. Consequently, osteoclast differentiation and activity are regulated by several systems. Because bone loss occurs when estrogen declines at the menopause, the modulation of osteoclast formation and activity by estrogen is an important issue. The mechanisms by which estrogen regulates bone turnover remain unclear [1]. *Corresponding author: Lisa J. Robinson, 707 Scaife Hall, University of Pittsburgh, Pittsburgh, PA 15261, Tel: +1 412 647-0365, Fax: +1 412 647-4008, robinsonlj@msx.upmc.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptUnresolved issues include whether estrogen causes apoptosis of osteoclasts or osteoclast precursors, and whether estrogen suppresses osteoclast formation directly or whether effects are mediated via oth...

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“…How exactly excessive PKG activity induces cell death is not clear, although this may involve phosphorylation of VASP, which, apart from regulating cell migration, has also been linked to cell death (Deguchi et al, 2002;Hou et al, 2006). Moreover, PKG-dependent VASP phosphorylation has been shown to mediate activation of calpains in osteoclasts (Yaroslavskiy et al, 2007). In this study on the cpfl1 retina and in previous studies on the rd1 mouse (Paquet-Durand et al, 2006, 2007a (Wingrave et al, 2004;Sanges et al, 2006;Cao et al, 2007), this finding raises the possibility of also using them for the prevention of cone cell death.…”

Section: Cgmp and Cone Migrationmentioning

confidence: 99%

cGMP‐dependent cone photoreceptor degeneration in the cpfl1 mouse retina

Trifunović

Dengler

Michalakis

et al. 2010

J of Comparative Neurology

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Inherited retinal degeneration affecting both rod and cone photoreceptors constitutes one of the leading causes of blindness in the developed world. Such degeneration is at present untreatable, and the underlying neurodegenerative mechanisms are unknown, even though certain genetic causes have been established. The rd1 mouse is one of the best characterized animal models for rod photoreceptor degeneration, whereas the cpfl1 mouse is a recently discovered model for cone cell death. Because both animal models are affected by functionally similar mutations in the rod and cone phosphodiesterase 6 genes, respectively, we asked whether the mechanisms of photoreceptor degeneration in these two mouse lines share common pathways. In the present study, we followed the temporal progression of photoreceptor degeneration in the cpfl1 retina, correlated it with specific metabolic markers, and compared it with the wild-type and the rd1 situation. Similar to corresponding rd1 observations, cpfl1 cone photoreceptor cell death was associated with an accumulation of cyclic guanosine monophosphate (cGMP), activity of calpains, and phosphorylation of vasodilator-stimulated protein (VASP). Cone degeneration progressed rapidly, with a peak in cell death around postnatal day 24. Furthermore, cpfl1 cone photoreceptor migration during early postnatal development was delayed significantly compared with the corresponding wild-type retina. The finding that rod and cone photoreceptor degeneration was associated with the same metabolic markers suggests that in both cell types similar degenerative mechanisms are active. This raises the possibility that equivalent neuroprotective strategies may be used to prevent both rod and cone photoreceptor degeneration.

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Necessity of inositol (1,4,5)-trisphosphate receptor 1 and μ-calpain in NO-induced osteoclast motility

Cited by 28 publications

References 53 publications

FSH-receptor isoforms and FSH-dependent gene transcription in human monocytes and osteoclasts

FSH-receptor isoforms and FSH-dependent gene transcription in human monocytes and osteoclasts

Estrogen inhibits RANKL-stimulated osteoclastic differentiation of human monocytes through estrogen and RANKL-regulated interaction of estrogen receptor-α with BCAR1 and Traf6

cGMP‐dependent cone photoreceptor degeneration in the cpfl1 mouse retina

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