Semaphorin 3B Is a 1,25-Dihydroxyvitamin D3-Induced Gene in Osteoblasts that Promotes Osteoclastogenesis and Induces Osteopenia in Mice
Open accessAbstract
The vitamin D endocrine system is important for skeletal homeostasis. 1,25-Dihydroxyvitamin D3 [1,25(OH)2D3] impacts bone indirectly by promoting intestinal absorption of calcium and phosphate and directly by acting on osteoblasts and osteoclasts. Despite the direct actions of 1,25(OH)2D3 in bone, relatively little is known of the mechanisms or target genes that are regulated by 1,25(OH)2D3 in skeletal cells. Here, we identify semaphorin 3B (SEMA3B) as a 1,25(OH)2D3-stimulated gene in osteoblastic cells. Northern analysis revealed strong induction of SEMA3B mRNA by 1,25(OH)2D3 in MG-63, ST-2, MC3T3, and primary osteoblastic cells. Moreover, differentiation of these osteogenic cells enhanced SEMA3B gene expression. Biological effects of SEMA3B in the skeletal system have not been reported. Here, we show that osteoblast-derived SEMA3B alters global skeletal homeostasis in intact animals and osteoblast function in cell culture. Osteoblast-targeted expression of SEMA3B in mice resulted in reduced bone mineral density and aberrant trabecular structure compared with nontransgenic littermates. Histomorphometry studies indicated that this was likely due to increased osteoclast numbers and activity. Indeed, primary osteoblasts obtained from SEMA3B transgenic mice stimulated osteoclastogenesis to a greater extent than nontransgenic osteoblasts. This study establishes that SEMA3B is a 1,25(OH)2D3-induced gene in osteoblasts and that osteoblast-derived SEMA3B impacts skeletal biology in vitro and in vivo. Collectively, these studies support a putative role for SEMA3B as an osteoblast protein that regulates bone mass and skeletal homeostasis.
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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 [175]
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- Authors
- Sutton, A. L. M., Zhang, X., Dowd, D. R., Kharode, Y. P., Komm, B. S., & MacDonald, P. N.
- Affiliations
- Case Western Reserve University (US)
- Wyeth (US)
- Corresponding author
- MacDonald, Paul N.
- Venue
- Molecular Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2008-06-01
- Volume
- 22
- Issue
- 6
- Pages
- 1370-1381
- ISSN
- 0888-8809 (ISSN-L)
- 1944-9917
- PMC
- PMC2422826
- OpenAlex
- W2090262533
- Cited by
- 61
- References
- 51
- Citations by year
- 2024: 1 · 2022: 3 · 2021: 3 · 2020: 4 · 2019: 4 · 2018: 7 · 2017: 2 · 2016: 5 · 2015: 4 · 2014: 6 · 2013: 4 · 2012: 7
- FWCI
- 1.51
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular Endocrinology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of General Medical Sciences (T32GM007250)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01-DK-53980, R01DK071769, R01DK053980, R01 DK71769)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (P30AR046031)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Health Sciences › Medicine › Pathology and Forensic Medicine › Vitamin D Research Studies
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
- Keywords
- SEMA3B, 1,25-dihydroxyvitamin D3, vitamin D, osteoblasts, osteoclastogenesis, osteopenia, bone mineral density, skeletal homeostasis, osteogenic differentiation, trabecular bone microarchitecture, transgenic mice
- MeSH terms
- Animals, Animals, Newborn, Bone and Bones, Bone Development, Bone Diseases, Metabolic, Calcitriol, Cells, Cultured, Chlorocebus aethiops, Female, Humans, Male, Membrane Glycoproteins, Mice, Inbred C57BL, Mice, Transgenic, Osteoblasts, Osteoclasts, Up-Regulation, COS Cells, Semaphorins, Mice, Cell Transdifferentiation
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