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Bromocriptine modulates the expression of PTHrP receptor, Indian hedgehog, and Runx2 proteins in the growth plate of lactating rats

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Abstract

In lactating rats, the endochondral bone growth is markedly enhanced, leading to the lengthening of long bone. This lactation-induced bone elongation could be abolished by a dopaminergic D2 receptor agonist bromocriptine, but how bromocriptine altered the expression of major chondroregulatory proteins in the growth plate cartilage was elusive. Here, we performed a quantitative immunohistochemical analysis to determine the expression of various peptides and transcription factors known to control the growth plate chondrocyte proliferation and differentiation [i.e., parathyroid hormone-related protein (PTHrP), PTHrP receptor, Indian hedgehog (Ihh), and runt-related transcription factor 2 (Runx2)], in bromocriptine-treated lactating rats. The results showed that bromocriptine markedly increased Ihh expression in hypertrophic chondrocytes during early and mid-lactation, while the expression of PTHrP receptor, but not its ligand PTHrP, was upregulated in the proliferative and hypertrophic zones during mid and late lactation. In contrast, the expression of Runx2, an important transcription factor for chondrocyte differentiation, was suppressed in the hypertrophic chondrocytes of bromocriptine-treated rats. In conclusion, bromocriptine increased Ihh and PTHrP receptor expressions and decreased Runx2 expression, which might, in turn, enhance chondrocyte proliferation and delay chondrocyte hypertrophy, thereby slowing down endochondral bone growth. This finding could explain how bromocriptine compromised the lactation-induced bone elongation.

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Acknowledgments

We thank Panan Suntornsaratoon for the excellent technical assistance. This work was supported by grants from the Thailand Research Fund, the Office of the Higher Education Commission, and the Faculty of Allied Health Sciences, Burapha University (MRG5480230 to K. Wongdee), and the Discovery-based Development Grant, National Science and Technology Development Agency (P-10-11281 to N. Charoenphandhu).

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The authors declare no conflicts of interest.

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Authors and Affiliations

  1. Office of Academic Management, Faculty of Allied Health Sciences, Burapha University, Chonburi, Thailand

    Kannikar Wongdee

  2. Center of Calcium and Bone Research (COCAB), Faculty of Science, Mahidol University, Bangkok, Thailand

    Kannikar Wongdee, Natchayaporn Thonapan, Wasana Saengamnart, Nateetip Krishnamra & Narattaphol Charoenphandhu

  3. Department of Physiology, Faculty of Science, Mahidol University, Rama VI Road, Bangkok, 10400, Thailand

    Natchayaporn Thonapan, Wasana Saengamnart, Nateetip Krishnamra & Narattaphol Charoenphandhu

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  1. Kannikar Wongdee
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  2. Natchayaporn Thonapan
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  5. Narattaphol Charoenphandhu
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Correspondence to Narattaphol Charoenphandhu.

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Wongdee, K., Thonapan, N., Saengamnart, W. et al. Bromocriptine modulates the expression of PTHrP receptor, Indian hedgehog, and Runx2 proteins in the growth plate of lactating rats. Mol Cell Biochem 381, 191–199 (2013). https://doi.org/10.1007/s11010-013-1702-y

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  • DOI: https://doi.org/10.1007/s11010-013-1702-y

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