Title |
Osteoblast Hypoxia-Inducible Factor-1α Pathway Activation Restrains Osteoclastogenesis via the Interleukin-33-MicroRNA-34a-Notch1 Pathway
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Published in |
Frontiers in immunology, October 2017
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DOI | 10.3389/fimmu.2017.01312 |
Pubmed ID | |
Authors |
Hui Kang, Kai Yang, Lianbo Xiao, Lei Guo, Changjun Guo, Yufei Yan, Jin Qi, Fei Wang, Bernhard Ryffel, Changwei Li, Lianfu Deng |
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. |
X Demographics
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Unknown | 1 | 100% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 1 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Unknown | 24 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Ph. D. Student | 5 | 21% |
Researcher | 4 | 17% |
Student > Bachelor | 2 | 8% |
Student > Master | 2 | 8% |
Student > Doctoral Student | 2 | 8% |
Other | 0 | 0% |
Unknown | 9 | 38% |
Readers by discipline | Count | As % |
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Medicine and Dentistry | 5 | 21% |
Biochemistry, Genetics and Molecular Biology | 3 | 13% |
Agricultural and Biological Sciences | 2 | 8% |
Immunology and Microbiology | 2 | 8% |
Pharmacology, Toxicology and Pharmaceutical Science | 1 | 4% |
Other | 0 | 0% |
Unknown | 11 | 46% |