Format

Send to

Choose Destination
Immun Inflamm Dis. 2016 Aug 2;4(3):338-49. doi: 10.1002/iid3.116. eCollection 2016 Sep.

The blocking of uPAR suppresses lipopolysaccharide-induced inflammatory osteoclastogenesis and the resultant bone loss through attenuation of integrin β3/Akt pathway.

Author information

1
Faculty of Pharmaceutical Science Department of Clinical Pathological Biochemistry Doshisha Women's College of Liberal Arts 97-1 Kodo Kyo-tanabe Kyoto 610-0395 Japan.
2
Division of Cellular Biosignal Sciences Department of Biochemistry Iwate Medical University 2-1-1 Nishitokuta, Yahaba-cho Shiwa-gun Iwate 028-3694 Japan.
3
Faculty of Medicine Kinki University 377-2 Ohnohigashi Osakasayama 589-8511 Japan.

Abstract

INTRODUCTION:

Chronic inflammatory diseases, such as rheumatoid arthritis and periodontitis, cause the bone destruction by promotion of the differentiation of monocyte/macrophage lineage cells into mature osteoclasts (OCs) with active bone-resorbing character. However, the detailed mechanisms underlying this disorder remain unclear. We herein investigated the role of urokinase plasminogen activator receptor (uPAR) in the bone destruction caused by chronic inflammation.

METHODS:

We investigated that the effect of uPAR on inflammatory OC formation induced by lipopolysaccharide (LPS) in inflammatory diseases.

RESULTS:

We found that the LPS more weakly induced OC formation and the resultant bone loss in uPAR-deficient mice than in wild-type mice. Additionally, we demonstrated that uPAR significantly potentiated LPS-induced OC formation of RAW264.7 mouse monocyte/macrophage linage cells in integrin β3/Akt-dependent manner. Moreover, we showed that the blocking of uPAR function by the administration of anti-uPAR neutralizing antibody significantly attenuated the LPS-induced OC formation and the resultant bone loss in mice.

CONCLUSIONS:

These results strongly suggest that uPAR negatively regulates the LPS-induced inflammatory OC formation and the resultant bone loss mediated through the integrin β3/Akt pathway. Our findings partly clarify the molecular mechanisms underlying bone destruction caused by chronic inflammatory diseases, and would benefit research on identifying antibody therapy for the treatment of these diseases.

KEYWORDS:

Inflammation; osteoclasts; uPAR

Supplemental Content

Full text links

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