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| Dikkopf-2, -3 and -4 Enhance Early Osteoblastic Differentiation
in Mouse Mesenchymal Progenitor Cells and Stimulate
Apoptosis in Osteoblastic Cells |
| 조선욱,정주연,선현진,양재연,김상완,김성연,신찬수 |
| 서울대학교 |
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| Abstract |
Objective
s: The inhibitory effect of Dickkopf (Dkk)-1 on osteoblastic differentiation through blocking Wnt signaling has
been well studied. However, the role of other members of the subfamily of Dkks remains unclear. We have examined the
role of different Dkks on osteoblastic differentiation of mesenchymal progenitor cells and apoptosis of osteoblasts.
Methods
Osteoblastic differentiation was induced by treatment of Wnt-3a with Dkks or vehicle in C3H10T1/2 cells and
alkaline phosphatase (ALP) activity was measured. Serum deprivation induced apoptosis was performed with pre-treatment
of Dkks or vehicle in MC3T3-E1 cells and methyl thiazolyl tetrazolium (MTT) assay was done.
Results
Dkk-2 at low concentrations (5 and 20 nM) and Dkk-3, -4 at any concentrations (5 to 100 nM) significantly
increased Wnt-3a-induced ALP activity, whereas Dkk-2 at high concentration (100 nM) significantly reduced. Treatment of
Dkk-2, -3 and -4 at high concentration (100 nM) showed significant decreases of Wnt/β-catenin transcriptional activity,
whereas no effects were seen at low concentration (20 nM). In parallel experiments, treatment of Dkk-1 showed robust dose
dependent inhibition not only in ALP activity but also in Wnt/β-catenin transcriptional activity. Dkk-2, -3 and -4 increased
serum deprivation-induced apoptosis in MC3T3-E1 mouse osteoblasts, while Dkk-1 had no effect.
Conclusions
We found that unlike Dkk-1, Dkk-3 and -4 stimulated early osteoblastic differentiation at various concentrations
regardless of their inhibitory effects on Wnt/β-catenin transcriptional activity at high concentration. Dkk-2 had a biphasic
effect where the lower doses significantly increased ALP activity while the high dose was inhibitory. Dkk-2, -3 and -4
stimulated osteoblast apoptosis whereas Dkk-1 had no effect. |
| Key Words:
Apoptosis, Dkk-2, Dkk-3, Dkk-4, Osteoblastic differentiation |
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