Possible involvement of elastase in enhanced osteoclast differentiation by neutrophils through degradation of osteoprotegerin

Sugisaki, Risa; Miyamoto, Yoichi; Yoshimura, Kentaro; Sasa, Kiyohito; Kaneko, Kotaro; Tanaka, Motohiro; Itose, Masakatsu; Inoue, Sakie; Baba, Kazuyoshi; Shirota, Tatsuo; Chikazu, Daichi; Kamijo, Ryutaro

Affiliations

¹Department of Biochemistry, Showa University School of Dentistry, Tokyo, Japan

²Department of Oral and Maxillofacial Surgery, Tokyo Medical University, Tokyo, Japan

³Department of Oral and Maxillofacial Surgery, Showa University School of Dentistry, Tokyo, Japan

⁴Department of Prosthodontics, Showa University School of Dentistry, Tokyo, Japan

Abstract and keywords

Neutrophils are one of the most abundant leukocytes in the sites of lesion of inflammatory diseases such as periodontitis and rheumatoid arthritis. These diseases are accompanied by bone loss, which worsens the quality of life of the patients. However, the role of neutrophils in the inflammatory bone loss has not been fully investigated. In the present study, we found that human neutrophils enhanced osteoclast differentiation from mouse bone marrow cells co-cultured with mouse osteoblasts in the presence of active vitamin D3. The enhanced osteoclast differentiation was significantly suppressed by elastatinal, a synthetic inhibitor of neutrophil elastase. Also, we found that human neutrophils degraded human recombinant osteoprotegerin (OPG), a decoy receptor for nuclear factor κB (RANK) ligand (RANKL), the essential osteoclast differentiation-inducing factor, expressed by osteoblasts. Degradation of OPG by neutrophils was suppressed by human α1-protease inhibitor, the major endogenous inhibitor of neutrophil elastase. Recombinant human neutrophil elastase degraded human OPG in its death domain-like region. These results indicated that the degradation of OPG by elastase contributed at least in part to the enhanced osteoclast differentiation by neutrophils. There is a possibility that neutrophils play an important role in inflammatory bone loss.

Keywords: Neutrophils; Elastase; Osteoprotegerin; Osteoclasts

Links

DOI: 10.1016/j.bone.2019.115216

PubMed: 31899346

WoS: 000510529200022

History

Received: 2019-10-21

Revised: 2019-12-18

Accepted: 2019-12-25

Online: 2019-12-31

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Cited By (1)

Year	Entry
2020	Nagy EE. Elastase mediated-degradation of osteoprotegerin: possible pitfalls and functional relevance. Bone. April 2020;133:115256.