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

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.