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Deletion of β1 Integrins from Cortical Osteocytes Reduces Load-Induced Bone Formation

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Abstract

Since integrins were first described as cell adhesion receptors over two decades ago, our understanding of their binding specificity and functional capacity has evolved dramatically. A number of in vitro cell culture experiments have suggested that integrins may play a role in the response of bone cells to mechanical stimuli. To determine whether the loss of integrins in bone cells affects mechanical adaptation in vivo, we used an ulnar loading model in mice with an osteocyte-specific β1 integrin deficiency. Using a Cre-loxP strategy in which Cre was driven by the 2.3 kb ColI(α1) promoter, the β1 integrin subunit was deleted from cortical osteocytes in mature (16 week old) mice. While there was no observable skeletal phenotype as a result of β1 integrin deletion, we found that conditional knockout mice exhibited a significant reduction in bone formation rates at the ulnar midshaft in response to three consecutive days of cyclic loading compared to floxed control mice. Further, there was a greater increase in periosteal expansion in control vs. conditional knockout mice in response to loading. While there are likely multiple signaling pathways involved in the cellular response to physical stimuli, our results suggest that β1 integrins play a role in mechanically induced bone formation.

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Abbreviations

cKO:

Conditional knockout

ColI(α1):

Type I collagen α1(I)

MAR:

Mineral apposition rate

MS/BS:

Mineralizing surface

BFR:

Bone formation rate

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Acknowledgments

The authors thank Dr. Ruth Globus, Dr. Jonathan Phillips, and Rose Mojarrab at NASA Ames Research Center, and Sara Temiyasathit at Stanford University for significant technical assistance and intellectual contributions. Funding sources included NIH Grant AR45989; NIH Grant AR54156; the US Department of Veterans Affairs; a National Science Foundation Graduate Research Fellowship; and a Veterans Affairs Pre-Doctoral Associated Health Rehabilitation Research Fellowship.

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Authors and Affiliations

  1. Bone and Joint Rehabilitation R&D Center, Veterans Affairs Medical Center, Palo Alto, CA, USA

    Julie B. Litzenberger, Weishene Joyce Tang, Alesha B. Castillo & Christopher R. Jacobs

  2. Department of Bioengineering, Stanford University, Stanford, CA, USA

    Julie B. Litzenberger & Christopher R. Jacobs

  3. Department of Mechanical Engineering, Stanford University, Stanford, CA, USA

    Alesha B. Castillo & Christopher R. Jacobs

  4. Department of Biomedical Engineering, Columbia University, 500 W. 120th Street, 351 Engineering Terrace, New York, NY, 10027, USA

    Christopher R. Jacobs

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  1. Julie B. Litzenberger
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Correspondence to Christopher R. Jacobs.

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Litzenberger, J.B., Tang, W.J., Castillo, A.B. et al. Deletion of β1 Integrins from Cortical Osteocytes Reduces Load-Induced Bone Formation. Cel. Mol. Bioeng. 2, 416–424 (2009). https://doi.org/10.1007/s12195-009-0068-4

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  • DOI: https://doi.org/10.1007/s12195-009-0068-4

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