EphrinB2 Regulation by PTH and PTHrP Revealed by Molecular Profiling in Differentiating Osteoblasts
Open accessAbstract
With the aim of identifying new pathways and genes regulated by PTH(1–34) and PTH-related protein 1–141 [PTHrP(1–141)] in osteoblasts, this study was carried out using a mouse marrow stromal cell line, Kusa 4b10, that acquires features of the osteoblastic phenotype in long-term culture conditions. After the appearance of functional PTH receptor 1 (PTHR1) in Kusa 4b10 cells, they were treated with either PTH(1–34) or PTHrP(1–141), and RNA was subjected to Affymetrix whole mouse genome array. The microarray data were validated using quantitative real-time RT-PCR on independently prepared RNA samples from differentiated Kusa 4b10, UMR106 osteosarcoma cells, and primary mouse calvarial osteoblasts, as well as in vivo using RNA from metaphyseal bone after a single PTH injection to 3-wk-old and 6-mo-old ovariectomized rats. Of the 45,101 probes used on the microarray, 4675 were differentially expressed by ≥1.5 fold, with a false discovery rate <0.1. Among the regulated genes, ephrinB2 mRNA was upregulated in response to both PTH and PTHrP. This was confirmed by quantitative real-time PCR in vitro and in vivo. Increased ephrinB2 protein was also shown in vitro by Western blotting, and immunostaining of femur sections showed ephrinB2 in both osteoclasts and osteoblasts. Production of ephrinB2, as well as other ephrins or Eph family members, did not change during differentiation of Kusa 4b10 cells. Blockade of ephrinB2/EphB4 interaction resulted in inhibition of mineralization of Kusa 4b10 cells. Together with the shown effect of ephrinB2 promoting osteoblast differentiation and bone formation through action on EphB4, the data raise the possibility that PTH or PTHrP might regulate ephrinB2 to act in a paracrine or autocrine manner on EphB4 or EphB2 in the osteoblast, contributing as a local event to the anabolic action of PTH or PTHrP.
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EphrinB2 is also expressed in osteoblasts.
“In addition, it has been shown that ephrinB2 is also expressed in osteoblasts [179].”
From Biology of Bone Tissue: Structure, Function, and Factors That Influence Bone Cells (2015) · cites this paper as [179]
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- Authors
- Allan, E. H., Häusler, K. D., Wei, T., Gooi, J. H., Quinn, J. M., Crimeen-Irwin, B., Pompolo, S., Sims, N. A., Gillespie, M. T., Onyia, J. E., & Martin, T. J.
- Affiliations
- The University of Melbourne (AU)
- Bone Joint and Cancer Unit, St Vincent's Institute, and Department of Medicine, University of Melbourne, Fitzroy, Victoria, Australia
- Eli Lilly (United States) (US)
- Corresponding author
- Martin, T John
- Venue
- Journal of Bone and Mineral Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2008-08-01
- Volume
- 23
- Issue
- 8
- Pages
- 1170-1181
- ISSN
- 0884-0431 (ISSN-L)
- 1523-4681
- OpenAlex
- W2044264310
- Cited by
- 199
- References
- 42
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 4 · 2023: 6 · 2022: 11 · 2021: 13 · 2020: 12 · 2019: 16 · 2018: 10 · 2017: 9 · 2016: 11 · 2015: 10 · 2014: 16 · 2013: 16 · 2012: 15
- FWCI
- 6.28
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- Journal of Bone and Mineral Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Health and Medical Research Council
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Health Sciences › Medicine › Nephrology › Parathyroid Disorders and Treatments
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
- Keywords
- ephrin-B2, parathyroid hormone, PTH-related protein, osteogenic differentiation, EphB4, EphB2, Eph/ephrin signaling, bone mineralization, ovariectomy, autocrine and paracrine regulation, gene expression profiling, bone formation, osteoclasts, UMR-106 cells
- MeSH terms
- Animals, Cell Differentiation, Cell Extracts, Cell Line, Dose-Response Relationship, Drug, Female, Colforsin, Gene Expression Regulation, Osteoblasts, Parathyroid Hormone, Blotting, Western, Reproducibility of Results, Rats, Sprague-Dawley, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, Ephrin-B2, Parathyroid Hormone-Related Protein, Mice, Rats
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