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Ghrelin stimulates proliferation of human osteoblastic TE85 cells via NO/cGMP signaling pathway

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Abstract

Ghrelin regulates bone formation and osteoblast proliferation, but the detailed signaling pathway for its action on osteoblasts remains unclear. In human osteoblastic TE85 cells, we observed the effects and intracellular signaling pathway of ghrelin on cell proliferation using BrdU incorporation method. Ghrelin, at 10−10–10−8 M concentration, significantly increased BrdU incorporation into TE85 cells. The action of ghrelin was inhibited by d-Lys3-GHRP-6, a selective antagonist of GHS-R. Nitric oxide (NO) scavenger hemoglobin and the NO synthase inhibitor NAME eliminated the stimulatory action of ghrelin on proliferation, while NO donor SNAP and NO synthase substrate L-AME stimulated proliferation of osteoblastic TE85 cells. The cGMP analogue, 8-Br-cGMP, stimulated TE85 cell proliferation, and ghrelin did not enhance proliferation in the presence of 8-Br-cGMP. Inhibition of cGMP production by the guanylate cyclase inhibitor prevented ghrelin-induced osteoblastic TE85 cell proliferation. In conclusion, ghrelin stimulates proliferation of human osteoblastic TE85 cells via intracellular NO/cGMP signaling pathway.

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Acknowledgement

This work is supported by the National Natural Science Foundation of China (No. 30300413 and No. 30471738).

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Authors and Affiliations

  1. Department of Orthopedics, Xijing Hospital, Fourth Military Medical University, Xi’an, 710032, China

    Deng-Hu Wang, Jun-Jie Du & Yun-Yu Hu

  2. Department of Orthopedics, Tangdu Hospital, Fourth Military Medical University, Xi’an, 710032, China

    Yun-Sheng Hu

  3. Research Center for Tumor, Guangzhou First Municipal People’s Hospital, Affiliated Guangzhou Medical College, Guangzhou, 510180, China

    Wei-De Zhong

  4. State Key Laboratory of Cancer Biology, Xijing Hospital, Fourth Military Medical University, Xi’an, 710032, China

    Wei-Jun Qin

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  1. Deng-Hu Wang
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  2. Yun-Sheng Hu
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Correspondence to Wei-Jun Qin.

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The authors Deng-Hu Wang and Yun-Sheng Hu contributed equally to this work.

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Wang, DH., Hu, YS., Du, JJ. et al. Ghrelin stimulates proliferation of human osteoblastic TE85 cells via NO/cGMP signaling pathway. Endocr 35, 112–117 (2009). https://doi.org/10.1007/s12020-008-9117-3

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  • DOI: https://doi.org/10.1007/s12020-008-9117-3

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