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Deletion of Cx43 from Osteocytes Results in Defective Bone Material Properties but Does Not Decrease Extrinsic Strength in Cortical Bone

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Abstract

Deletion of connexin (Cx) 43 from osteoblasts and osteocytes (OCN-Cre;Cx43fl/− mice) or from osteocytes only (DMP1-8kb-Cre;Cx43fl/fl mice) results in increased cortical, but not cancellous, osteocyte apoptosis and widening of the femoral midshaft without changes in cortical thickness. Despite the consequent larger moment of inertia, stiffness and ultimate load, measures of mechanical strength assessed by three-point bending, are not higher in either model of Cx43 deficiency due to reduced Young’s modulus, a measure of the stiffness of the material per unit of area. In OCN-Cre;Cx43fl/− mice, this was accompanied by a reduced ratio of nonreducible/reducible collagen cross-links as assessed by Fourier transformed infrared imaging (FTIRI) in the femoral diaphysis. On the other hand, DMP1-8kb-Cre;Cx43fl/fl mice did not show a significant reduction in collagen maturation in the same skeletal site, but a small decrease in mineralization was detected by FTIRI. Remarkably, both osteoblastic and osteocytic cells lacking Cx43 expressed lower mRNA levels of lysyl oxidase, a crucial enzyme involved in collagen maturation. These findings suggest that Cx43 expression in osteoblasts is involved in maintaining the quality of the bone matrix in cortical bone through the maturation of collagen cross-links. Osteocytic Cx43 expression is important also to maintain the stiffness of the bone material, where Cx43 deficiency results in local reduction in mineralization, possibly due to osteocyte apoptosis.

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Acknowledgments

The authors thank Kanan Vyas, Drs. Keith Condon and Ignacio Aguirre for technical assistance, and Drs. Charles Tuner, David Burr, and Matthew Allen for insightful suggestions. This research was supported by the National Institutes of Health (R01-AR053643). μCT studies were performed using equipment obtained with NIH grant S10-RR023710 (PI: James Williams, Department of Anatomy and Cell Biology, Indiana University School of Medicine).

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Authors and Affiliations

  1. Department of Anatomy & Cell Biology, Indiana University School of Medicine, 635 Barnhill Drive, MS-5035, Indianapolis, IN, 46202-5120, USA

    Nicoletta Bivi & Lilian I. Plotkin

  2. Department of Biology, Indiana University Purdue University Indianapolis, Indianapolis, IN, USA

    Mark T. Nelson & Jiliang Li

  3. National Synchrotron Light Source, Brookhaven National Laboratory, Upton, NY, USA

    Meghan E. Faillace & Lisa M. Miller

  4. Department of Biomedical Engineering, Stony Brook University, Stony Brook, NY, USA

    Meghan E. Faillace & Lisa M. Miller

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  1. Nicoletta Bivi
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Correspondence to Lilian I. Plotkin.

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Bivi, N., Nelson, M.T., Faillace, M.E. et al. Deletion of Cx43 from Osteocytes Results in Defective Bone Material Properties but Does Not Decrease Extrinsic Strength in Cortical Bone. Calcif Tissue Int 91, 215–224 (2012). https://doi.org/10.1007/s00223-012-9628-z

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  • DOI: https://doi.org/10.1007/s00223-012-9628-z

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