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Molecules and signaling pathways involved in the expression of OC-STAMP during osteoclastogenesis

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Abstract

The receptor activator of nuclear factor-κB ligand (RANKL) is a key factor in regulating osteoclastogenesis and in maintaining the survival of mature osteoclasts. We screened differentially expressed genes in RAW264.7 cells in response to RANKL and found osteoclast stimulatory transmembrane protein (OC-STAMP) as one of the RANKL-induced genes of interest. Recently, OC-STAMP has been identified as the RANKL-induced protein that promotes osteoclast differentiation, but the mechanism that regulates its expression is not understood. Therefore, the tissue distribution of OC-STAMP and the signaling pathways that regulate its expression were studied here. Similar to osteoclasts, OC-STAMP was expressed in most tissues, suggesting its involvement in the function of other tissues. Interestingly, OC-STAMP was downregulated by 17β-estradiol at high concentrations, suggesting the potential relationship between OC-STAMP and estrogen. Importantly, the knockdown of OC-STAMP at the transcript level resulted in the inhibition of multinucleated osteoclast formation and the decreased expression of genes including transcription factor (such as c-Jun), receptors (such as RANK and c-Fms), a signaling molecule (such as TRAF6), and a cell fusion-related molecule (such as meltrin-α), suggesting that the osteoclast differentiation needs the coordinated expression of OC-STAMP with several molecules required for transcription, signaling transduction, and cell fusion. Additionally, the treatment of its specific antibody inhibited the formation and bone resorptive activity of mature osteoclasts, suggesting its involvement in the function of mature osteoclasts. Furthermore, studies with pharmacological inhibitors suggested PKCβ or Akt might be the major signaling molecules to regulate the expression of OC-STAMP during osteoclastogenesis.

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Acknowledgments

We thank Prof. Paul R. Odgren and Ms. Hong Jia (Department of Cell Biology, University of Massachusetts Medical School, Worcester, MA, USA) for providing OC-STAMP specific antibody. This study was supported by a grant from the Korea Healthcare Technology R&D Project, Ministry of Health, Welfare & Family Affairs, Republic of Korea (A084242).

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Authors and Affiliations

  1. Laboratory of Chemical Genomics, Pharmacology Research Center, Korea Research Institute of Chemical Technology, P.O. Box 107, Yuseong-gu, Daejeon, 305-600, Korea

    Myung Hee Kim, Mikyung Park, Seung-hwa Baek, Hye Joo Kim & Seong Hwan Kim

  2. Department of Chemistry, Seoul National University, Gwanak-gu, Seoul, 151-742, Korea

    Hye Joo Kim

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  1. Myung Hee Kim
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Correspondence to Seong Hwan Kim.

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Kim, M.H., Park, M., Baek, Sh. et al. Molecules and signaling pathways involved in the expression of OC-STAMP during osteoclastogenesis. Amino Acids 40, 1447–1459 (2011). https://doi.org/10.1007/s00726-010-0755-4

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