Suppressive effect of regucalcin on cell differentiation and mineralization in osteoblastic MC3T3‐E1 cells

Yamaguchi, Masayoshi; Kobayashi, Masaru; Uchiyama, Satoshi

doi:10.1002/jcb.20524

Cited by 14 publications

(26 citation statements)

References 42 publications

(32 reference statements)

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“…Over-expression of RGN in the rat hepatoma cell line H4-II-E was shown to suppress the expression of oncogenes c-myc, Haras, and c-src, and increase the expression of tumor suppressor genes p53 and Rb [23,24]. Recent studies in hepatoma cell lines also showed growth suppression effects by RGN [25,26]. Therefore, upregulation of RGN may provide the benefit of suppressing hepatocarcinogenesis in Sod1−/− mice, whereas reduced expression of RGN may have the opposite effect.…”

Section: Discussionmentioning

confidence: 99%

Identification of biomarkers associated with the development of hepatocellular carcinoma in CuZn superoxide dismutase deficient mice

et al. 2007

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To identify biomarkers associated with the development of hepatocellular carcinoma (HCC) in CuZn superoxide dismutase (CuZnSOD, Sod1) deficient mice, 2-DE followed by MS analysis was carried out with liver samples obtained from 18-month-old Sod1−/− and +/+ mice. The intra-cellular Ca binding protein, regucalcin (RGN), showed a divergent alteration in Sod1−/− samples. Whereas elevated RGN levels were observed in −/− samples with no obvious neoplastic changes, marked reduction in RGN was observed in −/− samples with fully developed HCC. GST mu1 (GSTM1), on the other hand, showed a significant increase only in the neoplastic regions obtained from Sod1−/− livers. No change in GSTM1 was observed in the surrounding normal tissues. Marked reduction was observed in two intracellular lipid transporters, fatty acid binding protein 1 (FABP1) and major urinary protein 11 and 8 (MUP 11&8), in Sod1−/− samples. Analysis of additional samples at 18−22 months of age showed a three-fold increase in enolase activities in Sod1−/− livers. Consistent with previous findings, carbonic anhydrase 3 (CAIII) levels were significantly reduced in Sod1−/− samples, and immunohistochemical analysis revealed that the reduction was not homogenous throughout the lobular structure in the liver.

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Section: Discussionmentioning

confidence: 99%

Identification of biomarkers associated with the development of hepatocellular carcinoma in CuZn superoxide dismutase deficient mice

et al. 2007

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“…Regucalcin has been demonstrated to stimulate osteoclast-like cell formation in mouse marrow culture in vitro, and the protein stimulates bone resorption in rat femoral tissue in vitro (34). Also, regucalcin is found to have suppressive effects on cell differentiation and mineralization in osteoblastic MC3T3-E1 cells in vitro (35).…”

Section: Regulatory Effect Of Exogenous Regucalcin On Cell Function Imentioning

confidence: 99%

Regulatory effect of exogenous regucalcin on cell function in osteoblastic MC3T3-E1 cells: Involvement of intracellular signaling factor

Otomo

Yamaguchi²

2006

Int J Mol Med

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Bone loss is induced in regucalcin transgenic rats. The role of exogenous regucalcin in the regulation of osteoblastic cell function was investigated. Osteoblastic MC3T3-E1 cells with subconfluent monolayers were cultured for 24-72 h in medium containing regucalcin (10-10 or 10-9 M) without fetal bovine serum. The presence of regucalcin did not have a significant effect on cell number. Culture with regucalcin (10-9 M) for 24 h caused a significant decrease in protein and DNA contents in osteoblastic cells. The effect of regucalcin in decreasing cellular protein content was significantly inhibited in the presence of various kinase inhibitors including staurosporine (10-7 M), dibucaine (10-6 M), PD98059 (10-8 M), or wortmannin (10-8 M). Meanwhile, culture with regucalcin caused a significant decrease in cellular DNA content in the presence of various kinase inhibitors. The presence of regucalcin did not have a significant effect on protein and DNA contents in the cells cultured with cycloheximide (10-7 M), an inhibitor of protein synthesis, or 5,6-dichloro-1-ß-D-ribofuranosylbenzimidazole (10-6 M), an inhibitor of transcription activity; which each inhibitor caused a significant decrease in those contents. The effect of regucalcin in decreasing cellular protein content was seen in the presence of insulin-like growth factor-I (IGF-I; 10-9 or 10-8 M). Such an effect was not observed in cellular DNA content. The results of reverse transcription-polymerase chain reaction analysis with specific primers showed that the expression of Runx 2 (Cbfa 1) and alkaline phosphatase mRNAs in osteoblastic cells was significantly suppressed in the presence of regucalcin (10-10 or 10-9 M). Glyceraldhyde-3phosphate dehydrogenase mRNA level was not significantly changed with culture of regucalcin (10-10 or 10-9 M). This study supports the view that exogenous regucalcin regulates the function of osteoblastic cells, and that the effect of protein is mediated through signaling factors.

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“…Osteoblastic cell formation from bone marrow cells has been enhanced in regucalcin transgenic rats (36). Exogenous regucalcin has been shown to have stimulatory effects on osteoclastogenesis in bone marrow cell cultures (32) and suppressive effects on osteoblastic differentiation and mineralization in vitro (33). Regucalcin may play an important role in the regulation of bone metabolism.…”

Section: Discussionmentioning

confidence: 99%

“…The endogenous regucalcin in osteoblastic cells has suppressive effects on cell function that is involved in differentiation and mineralization (33). If regucalcin mRNA expression is regulated by various hormones and cytokines which are involved in the regulation of osteoblastic cell function, the endogenous regucalcin may be partly related, in light of hormone and cytokine effects on osteoblastic cells.…”

Section: Discussionmentioning

confidence: 99%

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Hormonal regulation of regucalcin mRNA expression in osteoblastic MC3T3-E1 cells

Yamaguchi

Otomo²,

Uchiyama³

et al. 2008

Int J Mol Med

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Abstract. The effect of various hormones on regucalcin mRNA expression in osteoblastic MC3T3-E1 cells in vitro was investigated. Cells with subconfluency were cultured for 24 or 48 h in a medium containing either vehicle or various hormones without fetal bovine serum. Regucalcin mRNA expression was significantly increased after culture with parathyroid hormone (synthetic human PTH; 10 -7 M), insulinlike growth factor-I (IGF-I; 10 -8 M), or 17ß-estradiol (10 -10 or 10 -9 M) for 48 h. Culture with 1,25-dihydroxyvitamin D 3 (10 -7 M) for 48 h caused a significant decrease in regucalcin mRNA expression. Regucalcin mRNA expression was significantly decreased after culture with tumor necrosis factor-α (1 or 10 ng/ml of medium) for 24 or 48 h. The effect of PTH or IGF-I in increasing regucalcin mRNA expression was not seen in the presence of staurosporine (10 -8 M), an inhibitor of protein kinase C, or PD98059 (10 -7 M), an inhibitor of mitosis-activated protein kinase (MAP kinase), respectively, suggesting that regucalcin mRNA expression is enhanced through intracellular signaling factors. This study demonstrated that regucalcin mRNA expression in osteoblastic MC3T3-E1 cells is regulated by various hormones.

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Suppressive effect of regucalcin on cell differentiation and mineralization in osteoblastic MC3T3‐E1 cells

Cited by 14 publications

References 42 publications

Identification of biomarkers associated with the development of hepatocellular carcinoma in CuZn superoxide dismutase deficient mice

Identification of biomarkers associated with the development of hepatocellular carcinoma in CuZn superoxide dismutase deficient mice

Regulatory effect of exogenous regucalcin on cell function in osteoblastic MC3T3-E1 cells: Involvement of intracellular signaling factor

Hormonal regulation of regucalcin mRNA expression in osteoblastic MC3T3-E1 cells

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