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Opposing effects of Sca-1+ cell-based systemic FGF2 gene transfer strategy on lumbar versus caudal vertebrae in the mouse

Gene Therapy volume 23, pages 500–509 (2016)Cite this article

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Abstract

Our previous work showed that a Sca-1+ cell-based FGF2 therapy was capable of promoting robust increases in trabecular bone formation and connectivity on the endosteum of long bones. Past work reported that administration of FGF2 protein promoted bone formation in red marrow but not in yellow marrow. The issue as to whether the Sca-1+ cell-based FGF2 therapy is effective in yellow marrow is highly relevant to its clinical potential for osteoporosis, as most red marrows in a person of an advanced age are converted to yellow marrows. Accordingly, this study sought to compare the osteogenic effects of this stem cell-based FGF2 therapy on red marrow-filled lumbar vertebrae with those on yellow marrow-filled caudal vertebrae of young adult W41/W41 mice. The Sca-1+ cell-based FGF2 therapy drastically increased trabecular bone formation in lumbar vertebrae, but the therapy not only did not promote bone formation but instead caused substantial loss of trabecular bone in caudal vertebrae. The lack of an osteogenic response was not due to insufficient engraftment of FGF2-expressing Sca-1+ cells or inadequate FGF2 expression in caudal vertebrae. Previous studies have demonstrated that recipient mice of this stem cell-based FGF2 therapy developed secondary hyperparathyroidism and increased bone resorption. Thus, the loss of bone mass in caudal vertebrae might in part be due to an increase in resorption without a corresponding increase in bone formation. In conclusion, the Sca-1+ cell-based FGF2 therapy is osteogenic in red marrow but not in yellow marrow.

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Acknowledgements

This work was supported in part by a Merit Review Entry Program grant from the Department of Veterans Affair Medical Research program. All work, except the irradiation procedure, was performed in facilities provided by the Department of Veterans Affairs.

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Authors and Affiliations

  1. Musculoskeletal Disease Center, Jerry L. Pettis Memorial VA Medical Center, Loma Linda, CA, USA

    K-H W Lau, S-T Chen, X Wang, S Mohan, J E Wergedal, C Kesavan & S L Hall

  2. Laboratory of Human Toxicology, Pharmacology, Applied/Developmental Research Directorate, SAIC-Frederick, Frederick National Laboratory for Cancer Research, Frederick, MD, USA

    A K Srivastava

  3. Department of Radiation Medicine, Loma Linda University School of Medicine, Loma Linda, CA, USA

    D S Gridley

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  1. K-H W Lau
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Correspondence to S L Hall.

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Lau, KH., Chen, ST., Wang, X. et al. Opposing effects of Sca-1+ cell-based systemic FGF2 gene transfer strategy on lumbar versus caudal vertebrae in the mouse. Gene Ther 23, 500–509 (2016). https://doi.org/10.1038/gt.2016.21

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