Quiescent Bone Lining Cells Are a Major Source of Osteoblasts During Adulthood
Open accessAbstract
The in vivo origin of bone-producing osteoblasts is not fully defined. Skeletal stem cells, a population of mesenchymal stem cells resident in the bone marrow compartment, are thought to act as osteoprogenitors during growth and adulthood. Quiescent bone lining cells (BLCs) have been suggested as a population capable of activation into mature osteoblasts. These cells were defined by location and their morphology and studies addressing their significance have been hampered by their inaccessibility, and lack of markers that would allow for their identification and tracing. Using lineage tracing models, we have observed labeled osteoblasts at time points extending beyond the reported lifespan for this cell type, suggesting continuous reactivation of BLCs. BLCs also make a major contribution to bone formation after osteoblast ablation, which includes the ability to proliferate. In contrast, mesenchymal progenitors labeled by Gremlin1 or alpha smooth muscle actin do not contribute to bone formation in this setting. BLC activation is inhibited by glucocorticoids, which represent a well-established cause of osteoporosis. BLCs express cell surface markers characteristic of mesenchymal stem/progenitors that are largely absent in osteoblasts including Sca1 and Leptin Receptor. BLCs also show different gene expression profiles to osteoblasts, including elevated expression of Mmp13, and osteoclast regulators RANKL and macrophage colony stimulating factor, and retain osteogenic potential upon transplantation. Our findings provide evidence that bone lining cells represent a major source of osteoblasts during adulthood.
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Osteoclasts initiate osteoprogenitor cell expansion by activating osteoprogenitor reservoirs located in proximity to the eroded bone surface consisting of BLCs, canopy cells and pericytes.
“A study by Matic et al.137 led to the development of a model in which osteoclasts initiate osteoprogenitor cell expansion (see following section) by activating osteoprogenitor reservoirs located in proximity to the eroded bone surface consisting of BLCs, canopy cells and pericytes.120”
From Bone remodeling: an operational process ensuring survival and bone mechanical competence (2022) · cites this paper as [137]
BLCs can also be osteoblast precursors and do not exclusively represent a final differentiation stage of the osteogenic line.
“BLCs do not exclusively represent a final differentiation stage of the osteogenic line; they can also be osteoblast precursors.137”
From Bone remodeling: an operational process ensuring survival and bone mechanical competence (2022) · cites this paper as [137]
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- Authors
- Matic, I., Matthews, B. G., Wang, X., Dyment, N. A., Worthley, D. L., Rowe, D. W., Grcevic, D., & Kalajzic, I.
- Affiliations
- Department of Reconstructive Sciences, University of Connecticut Health Center, Farmington, Connecticut, USA
- UConn Health (US)
- South Australian Health and Medical Research Institute (AU)
- Department of Physiology and Immunology, School of Medicine, University of Zagreb, Zagreb, Croatia
- Venue
- Stem Cells
- Publisher
- Oxford University Press (OUP)
- Published
- 2016-08-29
- Volume
- 34
- Issue
- 12
- Pages
- 2930-2942
- ISSN
- 1066-5099 (ISSN-L)
- 1549-4918
- PMC
- PMC5450652
- OpenAlex
- W2483820928
- Cited by
- 195
- References
- 46
- Citations by year
- 2026: 9 · 2025: 12 · 2024: 14 · 2023: 25 · 2022: 15 · 2021: 26 · 2020: 37 · 2019: 29 · 2018: 15 · 2017: 10 · 2016: 3
- FWCI
- 9.87
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- Stem Cells (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion)
- ResearchSpace (University of Auckland) (submittedVersion)
- Funders
- NIH/NIAMS (AR055607, K99 AR067283)
- Connecticut Regenerative Medicine Research Fund (14-SCA-UCHC-02)
- NIH/NIDCR (T90 DE021989)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
- Keywords
- bone lining cells, lineage tracing, mesenchymal stem cells, osteoprogenitors, glucocorticoids, osteoporosis, MMP-13, RANKL, macrophage colony-stimulating factor, spinocerebellar ataxia type 1, leptin receptor, bone formation, osteogenic potential
- MeSH terms
- Actins, Aging, Animals, Bone and Bones, Bone Marrow Cells, Cell Differentiation, Colony-Forming Units Assay, Glucocorticoids, Osteoblasts, Osteogenesis, Phenotype, Prednisolone, Biomarkers, Cytokines, Cell Lineage, Intercellular Signaling Peptides and Proteins, Mice, Mesenchymal Stem Cells
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