Bisphosphonate-induced differential modulation of immune cell function in gingiva and bone marrow in vivo: role in osteoclast-mediated NK cell activation

Oncotarget
Han-Ching TsengAnahid Jewett

Abstract

The aim of this study is to establish osteoclasts as key immune effectors capable of activating the function of Natural Killer (NK) cells, and expanding their numbers, and to determine in vivo and in vitro effect of bisphosphonates (BPs) during NK cell interaction with osteoclasts and on systemic and local immune function. The profiles of 27 cytokines, chemokines and growth factors released from osteoclasts were found to be different from dendritic cells and M1 macrophages but resembling to untreated monocytes and M2 macrophages. Nitrogen-containing BPs Zoledronate (ZOL) and Alendronate (ALN), but not non-nitrogen-containing BPs Etidronate (ETI), triggered increased release of pro-inflammatory mediators from osteoclasts while all three BPs decreased pit formation by osteoclasts. ZOL and ALN mediated significant release of IL-6, TNF-` and IL-1β, whereas they inhibited IL-10 secretion by osteoclasts. Treatment of osteoclasts with ZOL inhibited NK cell mediated cytotoxicity whereas it induced significant secretion of cytokines and chemokines. NK cells lysed osteoclasts much more than their precursor cells monocytes, and this correlated with the decreased expression of MHC class I expression on osteoclasts. Intravenous injection of...Continue Reading

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Citations

Feb 6, 2019·Frontiers in Immunology·Yu Du, Yongchang Wei
Aug 30, 2018·Current Osteoporosis Reports·J ChangL K McCauley
Apr 2, 2019·Frontiers in Endocrinology·Ilaria Roato, Massimo Vitale
Aug 10, 2018·The Journal of International Medical Research·Henrik HoltmannRita Depprich
Sep 5, 2021·The Journal of Evidence-based Dental Practice·Kumar KcManash Shrestha

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Methods Mentioned

BETA
ELISA
flow cytometry
ELISAs
PCR

Software Mentioned

FlowJo

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