uPA-derived peptide, Å6 is involved in the suppression of lipopolysaccaride-promoted inflammatory osteoclastogenesis and the resultant bone loss

Immun Inflamm Dis. 2017 Sep;5(3):289-299. doi: 10.1002/iid3.169. Epub 2017 May 11.

Abstract

Introduction: Chronic inflammatory diseases such as rheumatoid arthritis and periodontitis frequently cause bone destruction. Inflammation-induced bone loss results from the increase of bone-resorbing osteoclasts. Recently, we demonstrated that urokinase type plasminogen activator (uPA) suppressed lipopolysaccaride (LPS)-inflammatory osteoclastogenesis through the adenosine monophosphate-activated protein kinase (AMPK) pathway, whereas its receptor (uPAR) promoted that through the Akt pathway.

Methods: We investigated the effects of uPA-derived peptide (Å6) in the LPS-induced inflammatory osteoclastogenesis and bone destruction.

Results: We found that Å6 attenuated inflammatory osteoclastogenesis and bone loss induced by LPS in mice. We also showed that Å6 attenuated the LPS-promoted inflammatory osteoclastogenesis by inactivation of NF-κB in RAW264.7 mouse monocyte/macrophage lineage cells. Furthermore, we showed that Å6 attenuated the Akt phosphorylation, and promoted the AMPK phosphorylation.

Conclusion: Å6 is involved in the suppression of LPS-promoted inflammatory osteoclastgensis and bone destruction by regulating the AMPK and Akt pathways. These findings provide a basis for clinical strategies to improve the bone loss caused by inflammatory diseases.

Keywords: Bone loss; osteoclasts; uPA-derived peptide Å6.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinases / immunology
  • Animals
  • Bone Resorption / chemically induced
  • Bone Resorption / immunology
  • Bone Resorption / pathology
  • Bone Resorption / prevention & control*
  • Lipopolysaccharides / toxicity*
  • Mice
  • Osteoclasts / immunology*
  • Osteoclasts / pathology
  • Peptides / pharmacology*
  • Proto-Oncogene Proteins c-akt / immunology
  • Signal Transduction / drug effects*
  • Signal Transduction / immunology
  • Urokinase-Type Plasminogen Activator / pharmacology*

Substances

  • Lipopolysaccharides
  • Peptides
  • lipopolysaccharide, Escherichia coli O111 B4
  • Proto-Oncogene Proteins c-akt
  • AMP-Activated Protein Kinases
  • Urokinase-Type Plasminogen Activator