Cited by 19Bone Metabolism and DiseasesBone and Dental Protein StudiesOsteoarthritis Treatment and Mechanisms

Human Immunodeficiency Virus Type 1 Enhancer-binding Protein 3 Is Essential for the Expression of Asparagine-linked Glycosylation 2 in the Regulation of Osteoblast and Chondrocyte Differentiation

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Imamura, Katsuyuki, Maeda, Shingo, Kawamura, Ichiro, Matsuyama, Kanehiro, Shinohara, Naohiro, Yahiro, Yuhei, Nagano, Satoshi, Setoguchi, Takao +3 more·2014·Journal of Biological Chemistry

Abstract

Human immunodeficiency virus type 1 enhancer-binding protein 3 (Hivep3) suppresses osteoblast differentiation by inducing proteasomal degradation of the osteogenesis master regulator Runx2. In this study, we tested the possibility of cooperation of Hivep1, Hivep2, and Hivep3 in osteoblast and/or chondrocyte differentiation. Microarray analyses with ST-2 bone stroma cells demonstrated that expression of any known osteochondrogenesis-related genes was not commonly affected by the three Hivep siRNAs. Only Hivep3 siRNA promoted osteoblast differentiation in ST-2 cells, whereas all three siRNAs cooperatively suppressed differentiation in ATDC5 chondrocytes. We further used microarray analysis to identify genes commonly down-regulated in both MC3T3-E1 osteoblasts and ST-2 cells upon knockdown of Hivep3 and identified asparagine-linked glycosylation 2 (Alg2), which encodes a mannosyltransferase residing on the endoplasmic reticulum. The Hivep3 siRNA-mediated promotion of osteoblast differentiation was negated by forced Alg2 expression. Alg2 suppressed osteoblast differentiation and bone formation in cultured calvarial bone. Alg2 was immunoprecipitated with Runx2, whereas the combined transfection of Runx2 and Alg2 interfered with Runx2 nuclear localization, which resulted in suppression of Runx2 activity. Chondrocyte differentiation was promoted by Hivep3 overexpression, in concert with increased expression of Creb3l2, whose gene product is the endoplasmic reticulum stress transducer crucial for chondrogenesis. Alg2 silencing suppressed Creb3l2 expression and chondrogenesis of ATDC5 cells, whereas infection of Alg2-expressing virus promoted chondrocyte maturation in cultured cartilage rudiments. Thus, Alg2, as a downstream mediator of Hivep3, suppresses osteogenesis, whereas it promotes chondrogenesis. To our knowledge, this study is the first to link a mannosyltransferase gene to osteochondrogenesis.

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Authors
Imamura, K., Maeda, S., Kawamura, I., Matsuyama, K., Shinohara, N., Yahiro, Y., Nagano, S., Setoguchi, T., Yokouchi, M., Ishidou, Y., & Komiya, S.
Affiliations
Kagoshima University (JP)
Corresponding author
Maeda, Shingo
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2014-04
Volume
289
Issue
14
Pages
9865-9879
ISSN
0021-9258 (ISSN-L)
OpenAlex
W1996918240
Cited by
19
References
43
Citations by year
2025: 1 · 2023: 2 · 2022: 4 · 2020: 2 · 2019: 3 · 2018: 1 · 2017: 1 · 2016: 2 · 2015: 3
FWCI
0.82
Type
journal article
Language
en
Open access
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
Japan Society for the Promotion of Science (23592222, 23592221, 25462376)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
  • Health Sciences › Medicine › Rheumatology › Bone and Dental Protein Studies
  • Health Sciences › Medicine › Rheumatology › Osteoarthritis Treatment and Mechanisms
Keywords
ALG-2, mannosyltransferase, Runx2, osteogenic differentiation, chondrogenic differentiation, osteochondrogenesis, CREB3L2, endoplasmic reticulum stress, bone formation, MC3T3-E1 cells
MeSH terms
Animals, Cell Differentiation, Cell Line, Cell Nucleus, DNA-Binding Proteins, Mannosyltransferases, Osteoblasts, Osteogenesis, Gene Expression Regulation, Enzymologic, Chondrocytes, Active Transport, Cell Nucleus, Core Binding Factor Alpha 1 Subunit, Mice, Gene Knockdown Techniques, Endoplasmic Reticulum Stress

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