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Review
. 2023 May:170:116724.
doi: 10.1016/j.bone.2023.116724. Epub 2023 Mar 1.

Targeting osteocytes vs osteoblasts

Affiliations
Review

Targeting osteocytes vs osteoblasts

Y Kitase et al. Bone. 2023 May.

Abstract

Although osteoblasts and osteocytes are descended from the same lineage, they each have unique and essential roles in bone. Targeting gene deletion to osteoblasts and osteocytes using the Cre/loxP system has greatly increased our current understanding of how these cells function. Additionally, the use of the Cre/loxP system in conjunction with cell-specific reporters has enabled lineage tracing of these bone cells both in vivo and ex vivo. However, concerns have been raised regarding the specificity of the promoters used and the resulting off-target effects on cells within and outside of the bone. In this review, we have summarized the main mouse models that have been used to determine the functions of specific genes in osteoblasts and osteocytes. We discuss the expression patterns and specificity of the different promoter fragments during osteoblast to osteocyte differentiation in vivo. We also highlight how their expression in non-skeletal tissues may complicate the interpretation of study results. A thorough understanding of when and where these promoters are activated will enable improved study design and greater confidence in data interpretation.

Keywords: Cre/loxP; Differentiation; Osteoblasts; Osteocytes; Transgenic.

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Conflict of interest statement

Declaration of competing interest The authors have no financial competing interests to declare.

Figures

Figure 1.
Figure 1.. A summary of the promoters used to target osteoblasts and osteocytes in vivo.
The stage of differentiation, from osteoblast to mature osteocyte, at which the onset of promoter activity has been demonstrated in fluorescent reporter and Cre-mediated gene deletion studies. See text for specific references. Created with BioRender.com.

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References

    1. Kramer I, Halleux C, Keller H, Pegurri M, Gooi JH, Weber PB, Feng JQ, Bonewald LF, Kneissel M, Osteocyte Wnt/beta-catenin signaling is required for normal bone homeostasis, Mol Cell Biol 30(12) (2010) 3071–85. - PMC - PubMed
    1. Bivi N, Pacheco-Costa R, Brun LR, Murphy TR, Farlow NR, Robling AG, Bellido T, Plotkin LI, Absence of Cx43 selectively from osteocytes enhances responsiveness to mechanical force in mice, J Orthop Res 31(7) (2013) 1075–81. - PMC - PubMed
    1. Xiong J, Piemontese M, Onal M, Campbell J, Goellner JJ, Dusevich V, Bonewald L, Manolagas SC, O’Brien CA, Osteocytes, not Osteoblasts or Lining Cells, are the Main Source of the RANKL Required for Osteoclast Formation in Remodeling Bone, PLoS One 10(9) (2015) e0138189. - PMC - PubMed
    1. Powell WF Jr., Barry KJ, Tulum I, Kobayashi T, Harris SE, Bringhurst FR, Pajevic PD, Targeted ablation of the PTH/PTHrP receptor in osteocytes impairs bone structure and homeostatic calcemic responses, J Endocrinol 209(1) (2011) 21–32. - PMC - PubMed
    1. Clinkenbeard EL, Cass TA, Ni P, Hum JM, Bellido T, Allen MR, White KE, Conditional Deletion of Murine Fgf23: Interruption of the Normal Skeletal Responses to Phosphate Challenge and Rescue of Genetic Hypophosphatemia, J Bone Miner Res 31(6) (2016) 1247–57. - PMC - PubMed

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