A Class III Semaphorin (Sema3e) Inhibits Mouse Osteoblast Migration and Decreases Osteoclast Formation In Vitro
Open accessAbstract
Originally identified as axonal guidance cues, semaphorins are expressed throughout many different tissues and regulate numerous non-neuronal processes. We demonstrate that most class III semaphorins are expressed in mouse osteoblasts and are differentially regulated by cell growth and differentiation: Sema3d expression is increased and Sema3e expression decreased during proliferation in culture, while expression of Sema3a is unaffected by cell density but increases in cultures of mineralizing osteoblasts. Expression of Sema3a, -3e, and -3d is also differentially regulated by osteogenic stimuli; inhibition of GSK3β decreased expression of Sema3a and -3e, while 1,25-(OH)(2)D(3) increased expression of Sema3e. Parathyroid hormone had no effect on expression of Sema3a, -3b, or -3d. Osteoblasts, macrophages, and osteoclasts express the Sema3e receptor PlexinD1, suggesting an autocrine and paracrine role for Sema3e. No effects of recombinant Sema3e on osteoblast proliferation, differentiation, or mineralization were observed; but Sema3e did inhibit the migration of osteoblasts in a wound-healing assay. The formation of multinucleated, tartrate-resistant acid phosphatase-positive osteoclasts was decreased by 81% in cultures of mouse bone marrow macrophages incubated with 200 ng/mL Sema3e. Correspondingly, decreased expression of osteoclast markers (Itgb3, Acp5, Cd51, Nfatc1, CalcR, and Ctsk) was observed by qPCR in macrophage cultures differentiated in the presence of Sema3e. Our results demonstrate that class III semaphorins are expressed by osteoblasts and differentially regulated by differentiation, mineralization, and osteogenic stimuli. Sema3e is a novel inhibitor of osteoclast formation in vitro and may play a role in maintaining local bone homeostasis, potentially acting as a coupling factor between osteoclasts and osteoblasts.
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Semaphorins are involved in cell-cell communication between osteoclasts and osteoblasts during bone remodeling.
“In bone, it has been suggested that semaphorins are also involved in cell-cell communication between osteoclasts and osteoblasts during the bone remodeling cycle [174–176].”
From Biology of Bone Tissue: Structure, Function, and Factors That Influence Bone Cells (2015) · cites this paper as [176]
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- Authors
- Hughes, A., Kleine-Albers, J., Helfrich, M. H., Ralston, S. H., & Rogers, M. J.
- Affiliations
- University of Aberdeen (GB)
- Western General Hospital (GB)
- Corresponding author
- Hughes, Alun
- Helfrich, Miep H.
- Venue
- Calcified Tissue International
- Published
- 2012-01-07
- Volume
- 90
- Issue
- 2
- Pages
- 151-162
- ISSN
- 0171-967X (ISSN-L)
- 1432-0827
- PMC
- PMC3271215
- OpenAlex
- W2143107468
- Cited by
- 46
- References
- 45
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 5 · 2022: 2 · 2021: 4 · 2020: 6 · 2019: 4 · 2018: 2 · 2017: 6 · 2016: 1 · 2015: 5 · 2014: 1 · 2013: 7 · 2012: 1
- FWCI
- 1.80
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc
- Locations
- Calcified Tissue International (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, cc-by-nc)
- Funders
- Versus Arthritis (17285)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Axon Guidance and Neuronal Signaling
- Health Sciences › Medicine › Rheumatology › Bone and Dental Protein Studies
- Keywords
- semaphorin 3E, osteoblast migration, osteoclastogenesis, osteogenic differentiation, GSK3β, 1,25-dihydroxyvitamin D3, parathyroid hormone, PlexinD1, bone marrow-derived macrophages, bone homeostasis, osteoblast-osteoclast coupling, mineralization
- MeSH terms
- Animals, Cell Differentiation, Cell Movement, Cells, Cultured, Cytoskeletal Proteins, Glycoproteins, Membrane Proteins, Mice, Inbred C57BL, Osteoblasts, Osteoclasts, Rabbits, Blotting, Western, Reverse Transcriptase Polymerase Chain Reaction, Semaphorins, Mice, Real-Time Polymerase Chain Reaction
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