2-NPPA Mitigates Osteoclastogenesis via Reducing TRAF6-Mediated c-fos Expression

Excessive bone resorption leads to bone destruction in pathological bone diseases. Osteoporosis, which occurs when osteoclast-mediated bone resorption exceeds osteoblast-mediated bone synthesis, is regarded a global health challenge. Therefore, it is of great importance to identify agents that can r...

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Published inFrontiers in pharmacology Vol. 11; p. 599081
Main Authors Chen, Zhihao, Ding, Mina, Cho, Eunjin, Seong, Jihyoun, Lee, Sunwoo, Lee, Tae-Hoon
Format Journal Article
LanguageEnglish
Published Switzerland Frontiers Media S.A 26.01.2021
Subjects
acetamide
bone loss
c-fos
osteoclastogenesis
Pharmacology
TRAF6
c-fos
osteoclastogenesis
TRAF6
acetamide
bone loss
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Summary:Excessive bone resorption leads to bone destruction in pathological bone diseases. Osteoporosis, which occurs when osteoclast-mediated bone resorption exceeds osteoblast-mediated bone synthesis, is regarded a global health challenge. Therefore, it is of great importance to identify agents that can regulate the activity of osteoclasts and prevent bone diseases mediated mainly by bone loss. We screened compounds for this purpose and found that 2-(2-chlorophenoxy)-N-[2-(4-propionyl-1piperazinyl) phenyl] acetamide (2-NPPA) exhibited a strong inhibitory effect on osteoclastogenesis. 2-NPPA suppressed the mRNA and protein expression of several osteoclast-specific markers and blocked the formation of mature osteoclasts, reducing the F-actin ring formation and bone resorption activity. In a cell signaling point of view, 2-NPPA exhibited a significant inhibitory effect on the phosphorylation of nuclear factor kappa-B (NF-κB) and c-fos expression and prevented ovariectomy-induced bone loss . These findings highlighted the potential of 2-NPPA as a drug for the treatment of bone loss-mediated disorders.
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Edited by: Salvatore Salomone, University of Catania, Italy
Kim Mansky, University of Minnesota Twin Cities, United States
These authors have contributed equally to this work
This article was submitted to Experimental Pharmacology and Drug Discovery, a section of the journal Frontiers in Pharmacology
Reviewed by: Matthew Walsh, University of Pennsylvania, United States
ISSN:1663-9812
1663-9812
DOI:10.3389/fphar.2020.599081