A Useful Method to Evaluate Bone Resorption Inhibitors, Using Osteoclast-like Multinucleated Cells

Sugawara, Katsura; Hamada, Masato; Hosoi, Shinji; Tamaoki, Tatsuya

doi:10.1006/abio.1997.2474

Cited by 14 publications

(12 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These data suggested that the inhibitory eect of UCS15A on bone resorption was probably not due to cytotoxicity. Previous studies showed that herbimycin A, a well-known src inhibitor, inhibited bone resorption in this assay with an IC 50 of 0.6 mM but was cytotoxic with an IC 50 of 3 mM (Sugawara et al, 1998). Similarly, radicicol, another src inhibitor, inhibited bone resorption with an IC 50 of 1 mM but was cytotoxic with an IC 50 of 10 mM.…”

Section: Effects Of Ucs15a On Bone Resorption Activity Of Mncsmentioning

confidence: 60%

“…Osteoclast-like multinucleated cells (MNCs) were prepared in vitro and bone resorption activity of MNCs was measured as reported previously (Akatsu et al, 1992;Sugawara et al, 1998). Brie¯y, to induce osteoclast-like MNCs, osteoblastic cells obtained from newborn-mouse calvaria and bone marrow cells obtained from 8-week old mice were co-cultured in the presence of 1,25-dihydroxyvitamin D 3 (10 nM) and dexamethasone (100 nM) at 378C for 6 days in a humidi®ed atmosphere of 5% CO 2 .…”

Section: Bone Resorption Assaysmentioning

confidence: 99%

“…Cytotoxicity of UCS15A was evaluaetd by MTT assay (Mosmann, 1983;Sugawara et al, 1998) using mouse osteoblastic cells. Because it was dicult to isolate MNCs for cytotoxicity determination, osteoblastic cells were used instead.…”

Section: Cytotoxicity Determinationmentioning

confidence: 99%

See 2 more Smart Citations

UCS15A, a non-kinase inhibitor of Src signal transduction

et al. 2001

Self Cite

View full text Add to dashboard Cite

Src tyrosine kinase plays key roles in signal transduction following growth factor stimulation and integrinmediated cell-substrate adhesion. Since src-signal transduction defects are implicated in a multitude of human diseases, we have sought to develop new ways to identify small molecule inhibitors using a yeast-based, activatedsrc over-expression system. In the present study, we describe the identi®cation of a unique src-signal transduction inhibitor, UCS15A. UCS15A was found to inhibit the src speci®c tyrosine phosphorylation of numerous proteins in v-src-transformed cells. Two of these phosphoproteins were identi®ed as bona-®de src substrates, cortactin and Sam68. UCS15A diered from conventional src-inhibitors in that it did not inhibit the tyrosine kinase activity of src. In addition, UCS15A appeared to dier from src-destabilizing agents such as herbimycin and radicicol that destabilize src by interfering with Hsp90. Our studies suggest that UCS15A exerted its src-inhibitory eects by a novel mechanism that involved disruption of protein-protein interactions mediated by src. One of the biological consequences of src-inhibition by UCS15A was its ability to inhibit the bone resorption activity of osteoclasts in vitro. These data suggest that UCS15A may inhibit the bone resorption activity of osteoclasts, not by inhibiting src tyrosine kinase activity, but by disrupting the interaction of proteins associated with src, thereby modulating downstream events in the src signal transduction pathway. Oncogene (2001Oncogene ( ) 20, 2068Oncogene ( ± 2079

show abstract

Section: Effects Of Ucs15a On Bone Resorption Activity Of Mncsmentioning

confidence: 60%

Section: Bone Resorption Assaysmentioning

confidence: 99%

See 1 more Smart Citation

UCS15A, a non-kinase inhibitor of Src signal transduction

et al. 2001

Self Cite

View full text Add to dashboard Cite

show abstract

“…The supernatant was collected at the end of the experiment, and the total concentration of calcium in the supernatant was measured with an atomic absorption spectrometer (2100, PE company) (Sugawara et al, 1998).…”

Section: Calcium Ion Concentration Measurementmentioning

confidence: 99%

Effects of water extract ofCajanus cajanleaves on differentiation and function of primary osteoblasts and osteoclastsin vitro

Zhang¹,

Ba²,

Ji³

et al. 2009

Pharmaceutical Biology

View full text Add to dashboard Cite

“…In contrast, Sugawara et al reported a dose-dependent effect between 10 and 100 nM sCT [14]. The different culture models used may at least partially explain the differences.…”

Section: Discussionmentioning

confidence: 90%

A study of the antiresorptive activity of salmon calcitonin microspheres using cultured osteoclastic cells

Dani¹,

Raiche

Puleo

et al. 2002

AAPS PharmSciTech

View full text Add to dashboard Cite

The purpose of this study was to evaluate salmon calcitonin (sCT) microspheres in vitro for their antiresorptive activity using cultured osteoclastic cells. The antiresorptive activity of sCT-loaded microspheres, prepared from a low molecular weight hydrophilic poly (lactide-co-glycolide) polymer (PLGA), was studied using bone marrow culture cells harvested from juvenile rats and cultured on slices of devitalized bone for up to 4 weeks. The resorptive activity of osteoclastic cells was quantified in terms of number and type of resorption pits and total area of resorption. Microspheres containing 5.1% sCT released 70% peptide in 2 weeks and 88% in 4 weeks. All sCT treatments inhibited total resorptive activity. A dose-dependent decrease in resorption was observed with sCT microspheres at 2 weeks. The high dose (10 mg of microspheres) produced a 99.5% decrease in resorption at 3 weeks, while the low dose (1 mg) produced an 80% reduction. Exposure of cultures to soluble sCT and sCT-loaded microspheres caused a decrease in the number of large pits, which were the predominant type formed in control cultures. Thus, this system could serve as an in vitro method to evaluate the antiresorptive effect of PLGA-sCT microspheres.

show abstract

A Useful Method to Evaluate Bone Resorption Inhibitors, Using Osteoclast-like Multinucleated Cells

Cited by 14 publications

References 31 publications

UCS15A, a non-kinase inhibitor of Src signal transduction

UCS15A, a non-kinase inhibitor of Src signal transduction

Effects of water extract ofCajanus cajanleaves on differentiation and function of primary osteoblasts and osteoclastsin vitro

A study of the antiresorptive activity of salmon calcitonin microspheres using cultured osteoclastic cells

Contact Info

Product

Resources

About