IL-1β induces pathologically activated osteoclasts bearing extremely high levels of resorbing activity: A possible pathological subpopulation of osteoclasts, accompanied by suppressed expression of kindlin-3 and Talin-1

Takuma Shiratori, Yukari Kyumoto, Akiko Kukita, Norihisa Uehara, Jingqi Zhang, Kinuko Koda, Mako Kamiya, Tamer Badawy, Erika Tomoda, Xianghe Xu, Takayoshi Yamaza, Yasuteru Urano, Kiyoshi Koyano, Toshio Kukita

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5 Citations (Scopus)

Abstract

As osteoclasts have the central roles in normal bone remodeling, it is ideal to regulate only the osteoclasts performing pathological bone destruction without affecting normal osteoclasts. Based on a hypothesis that pathological osteoclasts form under the pathological microenvironment of the bone tissues, we here set up optimum culture conditions to examine the entity of pathologically activated osteoclasts (PAOCs). Through searching various inflammatory cytokines and their combinations, we found the highest resorbing activity of osteoclasts when osteoclasts were formed in the presence of M-CSF, receptor activator of NF-κB ligand, and IL-1β. We have postulated that these osteoclasts are PAOCs. Analysis using confocal laser microscopy revealed that PAOCs showed extremely high proton secretion detected by the acid-sensitive fluorescence probe Rh-PM and bone resorption activity compared with normal osteoclasts. PAOCs showed unique morphology bearing high thickness and high motility with motile cellular processes in comparison with normal osteoclasts. We further examined the expression of Kindlin-3 and Talin-1, essential molecules for activating integrin b-chains. Although normal osteoclasts express high levels of Kindlin-3 and Talin-1, expression of these molecules was markedly suppressed in PAOCs, suggesting the abnormality in the adhesion property. When whole membrane surface of mature osteoclasts was biotinylated and analyzed, the IL-1β-induced cell surface protein was detected. PAOCs could form a subpopulation of osteo-clasts possibly different from normal osteoclasts. PAOC-specific molecules could be an ideal target for regulating pathological bone destruction.

Original languageEnglish
Pages (from-to)218-228
Number of pages11
JournalJournal of Immunology
Volume200
Issue number1
DOIs
Publication statusPublished - Jan 1 2018

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Talin
Osteoclasts
Interleukin-1
Bone and Bones
Confocal Microscopy
Macrophage Colony-Stimulating Factor Receptors

All Science Journal Classification (ASJC) codes

  • Immunology

Cite this

IL-1β induces pathologically activated osteoclasts bearing extremely high levels of resorbing activity : A possible pathological subpopulation of osteoclasts, accompanied by suppressed expression of kindlin-3 and Talin-1. / Shiratori, Takuma; Kyumoto, Yukari; Kukita, Akiko; Uehara, Norihisa; Zhang, Jingqi; Koda, Kinuko; Kamiya, Mako; Badawy, Tamer; Tomoda, Erika; Xu, Xianghe; Yamaza, Takayoshi; Urano, Yasuteru; Koyano, Kiyoshi; Kukita, Toshio.

In: Journal of Immunology, Vol. 200, No. 1, 01.01.2018, p. 218-228.

Research output: Contribution to journalArticle

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AU - Kyumoto, Yukari

AU - Kukita, Akiko

AU - Uehara, Norihisa

AU - Zhang, Jingqi

AU - Koda, Kinuko

AU - Kamiya, Mako

AU - Badawy, Tamer

AU - Tomoda, Erika

AU - Xu, Xianghe

AU - Yamaza, Takayoshi

AU - Urano, Yasuteru

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