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Sclerostin expression in trabecular bone is downregulated by osteoclasts

Masanori Koide1, Teruhito Yamashita1, Kohei Murakami2

  • 1Division of Hard Tissue Research, Institute for Oral Science, Matsumoto Dental University, 1780 Gobara, Hiro-oka, Shiojiri, Nagano, 399-0781, Japan.

Scientific Reports
|August 15, 2020
PubMed

Insights

Osteoclasts promote trabecular bone turnover by downregulating sclerostin expression. This process involves Leukemia inhibitory factor (LIF) and is regulated by RANKL signaling, impacting bone formation.

Area of Science:

  • Bone Biology
  • Skeletal Physiology
  • Cell Signaling

Background:

  • Trabecular bone exhibits high turnover, while cortical bone has low turnover, but the regulatory mechanisms remain unclear.
  • Osteocytes secrete sclerostin, a Wnt/β-catenin signaling antagonist, inhibiting bone formation.
  • Leukemia inhibitory factor (LIF) from osteoclasts is known to suppress sclerostin and promote bone formation.

Purpose of the Study:

  • To investigate the role of osteoclasts in regulating sclerostin expression and bone turnover in trabecular bone.
  • To elucidate the involvement of Leukemia inhibitory factor (LIF) and RANKL signaling in this process.

Main Methods:

  • Utilized Sost reporter mice and C57BL/6 mice treated with anti-RANKL antibody.
  • Analyzed Tnfsf11 heterozygous (Rankl+/-) mice.
  • Examined gene and protein expression (sclerostin, LIF, β-catenin) in bone tissues and cultured osteoclasts.

Main Results:

  • Osteoclasts were found to downregulate sclerostin expression in trabecular bone, promoting bone turnover.
  • Anti-RANKL treatment reduced osteoclasts, LIF-positive cells, and increased sclerostin-positive cells, while decreasing β-catenin and bone formation.
  • Rankl+/- mice showed decreased LIF, increased sclerostin, and reduced β-catenin and bone formation in trabecular bone.
  • RANKL stimulation in cultured osteoclasts increased Lif mRNA expression.

Conclusions:

  • Osteoclasts play a crucial role in promoting trabecular bone turnover by downregulating sclerostin expression.
  • The RANKL-LIF signaling pathway mediates the suppression of sclerostin by osteoclasts, thereby influencing bone formation and turnover.

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