Format

Send to

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

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

Author information

1
Faculty of Pharmaceutical Science, Department of Clinical Pathological Biochemistry, Doshisha Women's Collage of Liberal Arts, Kyoto, Japan.
2
Department of Biochemistry, Iwate Medical University School of Dentistry, Morioka, Iwate, Japan.

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

PMID:
28493442
PMCID:
PMC5569370
DOI:
10.1002/iid3.169
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Wiley Icon for PubMed Central
Loading ...
Support Center