The Role of Sphingosine 1-Phosphate in Migration of Osteoclast Precursors; an Application of Intravital Two-Photon Microscopy
Open accessAbstract
Sphingosine-1-phosphate (S1P), a biologically active lysophospholipid that is enriched in blood, controls the trafficking of osteoclast precursors between the circulation and bone marrow cavities via G protein-coupled receptors, S1PRs. While S1PR1 mediates chemoattraction toward S1P in bone marrow, where S1P concentration is low, S1PR2 mediates chemorepulsion in blood, where the S1P concentration is high. The regulation of precursor recruitment may represent a novel therapeutic strategy for controlling osteoclast-dependent bone remodeling. Through intravital multiphoton imaging of bone tissues, we reveal that the bidirectional function of S1P temporospatially regulates the migration of osteoclast precursors within intact bone tissues. Imaging technologies have enabled in situ visualization of the behaviors of several players in intact tissues. In addition, intravital microscopy has the potential to be more widely applied to functional analysis and intervention.
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Bone marrow osteoclast hematopoietic stem cells expressing S1PR2 enter the circulation by binding S1P, a chemotactic lysophospholipid normally present in high concentrations in blood.
“Bone marrow osteoclast hematopoietic stem cells (HSCs) expressing type-2 receptor for sphingosine-1-phosphate (S1PR2) enter the circulation by binding sphingosine-1-phosphate (S1P), a chemotactic lysophospholipid normally present in high concentrations in blood [15,16].”
From Osteoclasts and Microgravity (2020) · cites this paper as [16]
The “Osteoclast precursors and S1P” section (page not provided) says S1PR2 activation moves osteoclast precursors from the bloodstream into bone marrow, the opposite of the claimed direction. The intravital-imaging section attributes their movement toward blood vessels to S1PR1-mediated chemotaxis. The paper does support that S1P is abundant in blood, but describes the precursors as macrophage/monocyte-lineage cells rather than hematopoietic stem cells. (LLM, conf=0.90)
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredHSCs may be recycled to the bone marrow by binding S1P to S1PR1 or stay at bone surfaces where they evolve into mature osteoclasts by binding M-CSF and RANKL produced primarily by osteoblasts, osteocytes, and stromal cells.
“HSCs may then be recycled to the bone marrow by binding S1P to type-1 receptors (S1PR1) or stay at bone surfaces where they evolve into mature osteoclasts by binding M-CSF and RANKL produced primarily by osteoblasts, osteocytes, and stromal cells [15,16] (Figure 2).”
From Osteoclasts and Microgravity (2020) · cites this paper as [16]
The ‘Application of intravital imaging to the analysis of cell behavior in bone’ section says S1PR1-mediated chemotaxis returns osteoclast precursors from bone tissue to blood vessels, not to bone marrow. It also reports that precursors remaining on bone surfaces can develop into mature osteoclasts. The paper discusses osteoclast precursors rather than HSCs and does not support the specified M-CSF/RANKL mechanism or the listed cellular sources. (LLM, conf=0.87)
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- Authors
- Ishii, T., Shimazu, Y., Nishiyama, I., Kikuta, J., & Ishii, M.
- Affiliations
- Immunology Frontier Research Center, The University of Osaka (JP)
- Corresponding author
- Ishii, Masaru
- Venue
- Molecules and Cells
- Publisher
- Elsevier BV
- Published
- 2011-05
- Volume
- 31
- Issue
- 5
- Pages
- 399-404
- ISSN
- 0219-1032 (ISSN-L)
- 1016-8478
- PMC
- PMC3887611
- OpenAlex
- W2086950944
- Cited by
- 32
- References
- 35
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 2 · 2023: 2 · 2022: 1 · 2021: 1 · 2020: 2 · 2019: 1 · 2018: 2 · 2017: 1 · 2016: 2 · 2015: 2 · 2014: 3 · 2013: 3 · 2012: 3
- FWCI
- 0.35
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Molecules and Cells (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sphingolipid Metabolism and Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
- Keywords
- sphingosine-1-phosphate, osteoclast precursors, cell migration, S1PR1, S1PR2, G protein-coupled receptors, chemorepulsion, chemotaxis, bone remodeling, bone marrow, intravital two-photon microscopy, lysophospholipids
- MeSH terms
- Animals, Cell Movement, Lysophospholipids, Microscopy, Osteoclasts, Sphingosine, Signal Transduction, Photons
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