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Formation of Tethers Linking the Epiphysis and Metaphysis Is Regulated by Vitamin D Receptor-Mediated Signaling

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Abstract

Rat tibial growth plates have X-ray opaque tethers that link the epiphysis and metaphysis and increase with age as the growth plate (GP) becomes thinner. To determine if tether formation is a regulated process of GP maturation, we tested the hypotheses that tether properties and distribution can be quantified by micro-computed tomography (microCT), that rachitic GPs typical of vitamin D receptor knockout (VDR−/−) mice have fewer tethers and altered tether distribution, and that tether formation is regulated by signaling via the VDR. Distal femoral GPs from VDR+/+ and VDR−/− 8-week-old mice were analyzed with microCT and then processed for decalcified and undecalcified histomorphometry. A wide range of parameters that assessed GP and tether geometry and morphology, along with tether distribution, were measured using both microCT and histology. Growth plates of 10-week-old VDR+/+ and VDR−/− mice on a high-calcium, phosphorus, lactose, and vitamin D3 rescue diet were also analyzed. Both microCT and histology showed tethers present throughout normal mice GPs, while reduction in tether number and volume percentage occurred in VDR−/− GPs with localization to the central region. Decreased shrinkage in the axial direction during decalcified histological processing correlated with tether formation, suggesting mechanical stability due to tethers. Tether formation increased greatly between 8 and 10 weeks. Rescue diets restored VDR−/− GP size but not tether volume percentage. Overall, these results demonstrate microCT imaging’s utility for analyzing tether formation and suggest that signaling via the VDR plays a pivotal role in tether formation.

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Acknowledgments

The authors thank Brandon Gray and Ayanna Miller for their help in developing the mouse growth plate tether map. This research was supported by grants from Children’s Healthcare of Atlanta and the Georgia Tech/Emory Center for the Engineering of Living Tissues (NSF EEC 9731643) as well as a National Science Foundation Graduate Research Fellowship (to C. S. D. L.).

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Authors and Affiliations

  1. Institute of Bioengineering and Bioscience, Georgia Institute of Technology, 315 Ferst Drive NW, Atlanta, GA, 30332-0363, USA

    Jida Chen, Christopher S. D. Lee, Rhima M. Coleman, John Y. Yoon, Robert E. Guldberg, Zvi Schwartz & Barbara D. Boyan

  2. Chongqing University, Chongqing, China

    Jida Chen

  3. Lehrstuhl fur Orthopadie, Universitatsklinikum Hamburg-Eppendorf, Hamburg, Germany

    Christoph H. Lohmann & Jozef Zustin

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  1. Jida Chen
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  2. Christopher S. D. Lee
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  9. Barbara D. Boyan
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Correspondence to Barbara D. Boyan.

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Chen, J., Lee, C.S.D., Coleman, R.M. et al. Formation of Tethers Linking the Epiphysis and Metaphysis Is Regulated by Vitamin D Receptor-Mediated Signaling. Calcif Tissue Int 85, 134–145 (2009). https://doi.org/10.1007/s00223-009-9259-1

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  • DOI: https://doi.org/10.1007/s00223-009-9259-1

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