Osteoblast Hypoxia-Inducible Factor-1α Pathway Activation Restrains Osteoclastogenesis via the Interleukin-33-MicroRNA-34a-Notch1 Pathway.

Abstract:

:Functional cross-talk between osteoblasts and osteoclasts is a key process for bone homeostasis. Although osteoblast hypoxia-inducible factor-1α (HIF-1α) pathway activation results in impaired osteoclastogenesis via the direct regulation of osteoprotegerin (OPG), it is unclear whether there are other efficient mediators are involved in osteoblast HIF-1α pathway activation-restrained osteoclast formation. In addition to upregulated OPG, we observed that osteoblast HIF-1α activation led to increased interleukin-33 (IL-33) expression, which was found to inhibit osteoclastogenesis. Mechanistically, HIF-1α facilitates IL-33 expression by binding to -1,504/-1,500 bp on the Il-33 promoter. IL-33, thereby, acts on bone marrow-derived monocytes (BMMs) to reduce their osteoclastic differentiation. Moreover, microRNA-34a-5p (miR-34a-5p)-inhibited Notch1 activation was observed to play a central role in this process. Thereby, the identification of IL-33-miR-34a-5p-Notch1 pathway in the inhibitory effect of osteoblast HIF-1α pathway on osteoclastogenesis uncovers a new mechanism for understanding the effects of HIF-1α on bone remodeling.

journal_name

Front Immunol

journal_title

Frontiers in immunology

authors

Kang H,Yang K,Xiao L,Guo L,Guo C,Yan Y,Qi J,Wang F,Ryffel B,Li C,Deng L

doi

10.3389/fimmu.2017.01312

subject

Has Abstract

pub_date

2017-10-16 00:00:00

pages

1312

issn

1664-3224

journal_volume

8

pub_type

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