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The Contribution of Perilacunar Composition and Mechanical Properties to Whole-Bone Mechanical Outcomes in Streptozotocin-Induced Diabetes

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Abstract

Osteocytes are the most abundant cell type in bone and remodel their local perilacunar matrix in response to a variety of stimuli and diseases. How the perilacunar composition and mechanical properties are affected by type 1 diabetes (T1D), and the contribution of these local changes to the decline in whole-bone functional properties that occurs with diabetes remains unclear. 12–14 week old C57/BL6 male mice were administered a series of low-dose streptozotocin injections and sacrificed at baseline (BL), 3 (D3) and 7 weeks (D7) following confirmation of diabetes, along with age-matched controls (C3, C7). Femora were then subjected to a thorough morphological (μCT), mechanical (four-point bending, nanoindentation), and compositional (HPLC for collagen cross-links, Raman spectroscopy) analysis at the whole-bone and local (perilacunar and intracortical) levels. At the whole-bone level, D7 mice exhibited 10.7% lower ultimate load and 26.4% lower post-yield work relative to C7. These mechanical changes coincided with 52.2% higher levels of pentosidine at D7 compared to C7. At the local level, the creep distance increased, while modulus and hardness decreased in the perilacunar region relative to the intracortical for D7 mice, suggesting a spatial uncoupling in skeletal adaptation. D7 mice also exhibited increased matrix maturity in the 1660/1690 cm−1 ratio at both regions relative to C7. The perilacunar matrix maturity was predictive of post-yield work (46%), but perilacunar measures were not predictive of ultimate load, which was better explained by cortical area (26%). These results show that diabetes causes local perilacunar composition perturbations that affect whole-bone level mechanical properties, implicating osteocyte maintenance of its local matrix in the progression of diabetic skeletal fragility.

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Acknowledgements

We would like to thank Gurjit Mandair for training and assistance with Raman spectroscopy, and Ken Kozloff for use of the nanoindentation system. This work was supported by was supported by T32 DE007057, and P30AR069620. The content of this work is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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  1. Department of Biomedical Engineering, College of Engineering, University of Michigan, Ann Arbor, MI, USA

    Morgan W. Bolger & David H. Kohn

  2. Department of Chemistry, College of Literature, Science and the Arts, University of Michigan, Ann Arbor, MI, USA

    Tara Tekkey

  3. Department of Biologic and Materials Sciences, School of Dentistry, University of Michigan, 1011 N. University Ave., Ann Arbor, MI, 48109, USA

    David H. Kohn

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Bolger, M.W., Tekkey, T. & Kohn, D.H. The Contribution of Perilacunar Composition and Mechanical Properties to Whole-Bone Mechanical Outcomes in Streptozotocin-Induced Diabetes. Calcif Tissue Int 113, 229–245 (2023). https://doi.org/10.1007/s00223-023-01098-9

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