Endocrinol Metab > Volume 22(6); 2007 > Article
Journal of Korean Endocrine Society 2007;22(6):411-418.
DOI: https://doi.org/10.3803/jkes.2007.22.6.411    Published online December 1, 2007.
Identification and Validation of the Relationship of the Anabolic Effect of Parathyroid Hormone with the Wnt/beta-catenin Canonical Pathway.
Se Hwa Kim, Juan Ji An, Yumie Rhee, Sung Kil Lim
1Department of Internal Medicine, Kwandong University College of Medicine, Korea.
2Institute of Endocrine Research, Yonsei University College of Medicine, Korea.
3Department of Internal Medicine, Yonsei University College of Medicine, Korea.
Abstract
BACKGROUND
It has been well established that daily injections of low dose parathyroid hormone (PTH) increase bone mass in animals and humans. However, the precise mechanisms by which PTH exerts its anabolic action on bone are incompletely understood. The canonical Wnt-b-catenin signaling pathway has recently been demonstrated to have an important role in bone cell function. In the present study, we have examined the interaction between the PTH and Wnt signaling pathways in mouse osteoblastic MC3T3-E1 cells. METHODS & RESULTS: MC3T3-E1 cells were treated with 0.01-0.84 micrometer recombinant PTH. beta-catenin expression was significantly increased after 30 minutes of exposure to PTH and reached a maximum 2.7 fold increase at 1 hr and expression then faded at 6 hrs. In addition, treatment with PTH increased nuclear accumulation of activated beta-catenin; the ratio between the nuclear to cytoplasmic protein was more than three fold at 30 minutes and beyond. Moreover, PTH stimulated T-cell factor/lymphoid enhancer factor (TCF/LEF) reporter gene activity in MC3T3-E1 cells. Confocal microscopy revealed nuclear translocation of beta-catenin by PTH as compared with a glycogen synthase kinase-3beta (GSK-3beta) inhibitor. CONCLUSION: These results suggest that the anabolic mechanism of PTH might be partially associated with the Wnt-canonical pathway. The appropriate target of another anabolic agent should be determined through further studies of this pathway.
Key Words: beta-catenin, Bone, Parathyroid hormone, TCF/LEF, Wnt-canonical pathway
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