Negative feedback loop of bone resorption by NFATc1-dependent induction of Cadm1

Shinya Nakamura, Takuma Koyama, Naohiro Izawa, Seitaro Nomura, Takanori Fujita, Yasunori Omata, Takashi Minami, Morio Matsumoto, Masaya Nakamura, Eriko Fujita-Jimbo, Takashi Momoi, Takeshi Miyamoto, Hiroyuki Aburatani, Sakae Tanaka

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Trimethylation of histone H3 lysine 4 and lysine 27 (H3K4me3 and H3K27me3) at gene promoter regions critically regulates gene expression. Key developmental genes tend to exhibit changes in histone modification patterns from the H3K4me3/H3K27me3 bivalent pattern to the H3K4me3 monovalent pattern. Using comprehensive chromatin immunoprecipitation followed by sequencing in bone marrow-derived macrophages (BMMs) and mature osteoclasts, we found that cell surface adhesion molecule 1 (Cadm1) is a direct target of nuclear factor of activated T cells 1 (NFATc1) and exhibits a bivalent histone pattern in BMMs and a monovalent pattern in osteoclasts. Cadm1 expression was upregulated in BMMs by receptor activator of nuclear factor kappa B ligand (RANKL), and blocked by a calcineurin/NFATc1 inhibitor, FK506. Cadm1-deficient mice exhibited significantly reduced bone mass compared with wild-type mice, which was due to the increased osteoclast differentiation, survival and bone-resorbing activity in Cadm1-deficient osteoclasts. These results suggest that Cadm1 is a direct target of NFATc1, which is induced by RANKL through epigenetic modification, and regulates osteoclastic bone resorption in a negative feedback manner.

Original languageEnglish
Article numbere0175632
JournalPLoS One
Volume12
Issue number4
DOIs
Publication statusPublished - 2017 Apr 1

Fingerprint

NFATC Transcription Factors
bone resorption
Cell Adhesion Molecules
osteoclasts
adhesion
Osteoclasts
Bone
Adhesion
T-lymphocytes
Macrophages
Feedback
Molecules
histones
bone marrow
Histones
RANK Ligand
macrophages
Lysine
cells
lysine

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Nakamura, S., Koyama, T., Izawa, N., Nomura, S., Fujita, T., Omata, Y., ... Tanaka, S. (2017). Negative feedback loop of bone resorption by NFATc1-dependent induction of Cadm1. PLoS One, 12(4), [e0175632]. https://doi.org/10.1371/journal.pone.0175632

Negative feedback loop of bone resorption by NFATc1-dependent induction of Cadm1. / Nakamura, Shinya; Koyama, Takuma; Izawa, Naohiro; Nomura, Seitaro; Fujita, Takanori; Omata, Yasunori; Minami, Takashi; Matsumoto, Morio; Nakamura, Masaya; Fujita-Jimbo, Eriko; Momoi, Takashi; Miyamoto, Takeshi; Aburatani, Hiroyuki; Tanaka, Sakae.

In: PLoS One, Vol. 12, No. 4, e0175632, 01.04.2017.

Research output: Contribution to journalArticle

Nakamura, S, Koyama, T, Izawa, N, Nomura, S, Fujita, T, Omata, Y, Minami, T, Matsumoto, M, Nakamura, M, Fujita-Jimbo, E, Momoi, T, Miyamoto, T, Aburatani, H & Tanaka, S 2017, 'Negative feedback loop of bone resorption by NFATc1-dependent induction of Cadm1', PLoS One, vol. 12, no. 4, e0175632. https://doi.org/10.1371/journal.pone.0175632
Nakamura S, Koyama T, Izawa N, Nomura S, Fujita T, Omata Y et al. Negative feedback loop of bone resorption by NFATc1-dependent induction of Cadm1. PLoS One. 2017 Apr 1;12(4). e0175632. https://doi.org/10.1371/journal.pone.0175632
Nakamura, Shinya ; Koyama, Takuma ; Izawa, Naohiro ; Nomura, Seitaro ; Fujita, Takanori ; Omata, Yasunori ; Minami, Takashi ; Matsumoto, Morio ; Nakamura, Masaya ; Fujita-Jimbo, Eriko ; Momoi, Takashi ; Miyamoto, Takeshi ; Aburatani, Hiroyuki ; Tanaka, Sakae. / Negative feedback loop of bone resorption by NFATc1-dependent induction of Cadm1. In: PLoS One. 2017 ; Vol. 12, No. 4.
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