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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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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Other craniofacial morphology-related genes such as DCHS2, HIVEP2, HIVEP3, FREM1, and FRAS1 harbor AHMCs.
“Other craniofacial morphology-related genes, such as DCHS2133, HIVEP2149, HIVEP3150, FREM1151, and FRAS1152 harbor AHMCs”
From A catalog of single nucleotide changes distinguishing modern humans from archaic hominins (2019) · cites this paper as [150]
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A catalog of single nucleotide changes distinguishing modern humans from archaic hominins
Kuhlwilm, M., & Boeckx, C. (2019) · Scientific Reports · doi:10.1038/s41598-019-44877-x · Cited by 108 · see citing works
- 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)
- PMC
- PMC3975031
- 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
- hybrid
- doi.org
- Licence
- 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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