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Synovial Fluid Interleukin-16 Contributes to Osteoclast Activation and Bone Loss through the JNK/NFATc1 Signaling Cascade in Patients with Periprosthetic Joint Infection

Authors
  • Chang, Yuhan1, 2
  • Hsiao, Yi-min1, 2
  • Hu, Chih-Chien1, 2
  • Chang, Chih-Hsiang1, 2, 3, 4
  • Li, Cai-Yan1
  • Ueng, Steve W. N.1, 2, 3
  • Chen, Mei-Feng1
  • 1 (S.W.N.U.)
  • 2 Department of Orthopedic Surgery, Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan
  • 3 College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan
  • 4 Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan
Type
Published Article
Journal
International Journal of Molecular Sciences
Publisher
MDPI AG
Publication Date
Apr 21, 2020
Volume
21
Issue
8
Identifiers
DOI: 10.3390/ijms21082904
PMID: 32326301
PMCID: PMC7215706
Source
PubMed Central
Keywords
License
Green

Abstract

Because of lipopolysaccharide (LPS)-mediated effects on osteoclast differentiation and bone loss, periprosthetic joint infection (PJI) caused by Gram-negative bacteria increases the risk of aseptic loosening after reimplantation. Synovial fluid interleukin-16 (IL-16) expression was higher in patients with PJI than in patients without joint infection. Thus, we explored the effects of IL-16 on bone. We investigated whether IL-16 modulates osteoclast or osteoblast differentiation in vitro. An LPS-induced bone loss mice model was used to explore the possible advantages of IL-16 inhibition for the prevention of bone loss. IL-16 directly activated p38 and c-Jun N-terminal kinase (JNK)/mitogen-activated protein kinase (MAPK) signaling and increased osteoclast activation markers, including tartrate-resistant acid phosphatase (TRAP), cathepsin K, and nuclear factor of activated T cells 1 (NFATc1). IL-16 directly caused monocytes to differentiate into TRAP-positive osteoclast-like cells through NFATc1 activation dependent on JNK/MAPK signaling. Moreover, IL-16 did not alter alkaline phosphatase activity or calcium deposition during osteoblastic differentiation. Finally, IL-16 inhibition prevented LPS-induced trabecular bone loss and osteoclast activation in vivo. IL-16 directly increased osteoclast activation through the JNK/NFATc1 pathway. IL-16 inhibition could represent a new strategy for treating infection-associated bone loss.

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