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A Trabecular Bone Explant Model of Osteocyte–Osteoblast Co-Culture for Bone Mechanobiology

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Abstract

The osteocyte network is recognized as the major mechanical sensor in the bone remodeling process, and osteocyte–osteoblast communication acts as an important mediator in the coordination of bone formation and turnover. In this study, we developed a novel 3D trabecular bone explant co-culture model that allows live osteocytes situated in their native extracellular matrix environment to be interconnected with seeded osteoblasts on the bone surface. Using a low-level medium perfusion system, the viability of in situ osteocytes in bone explants was maintained for up to 4 weeks, and functional gap junction intercellular communication (GJIC) was successfully established between osteocytes and seeded primary osteoblasts. Using this novel co-culture model, the effects of dynamic deformational loading, GJIC, and prostaglandin E2 (PGE2) release on functional bone adaptation were further investigated. The results showed that dynamical deformational loading can significantly increase the PGE2 release by bone cells, bone formation, and the apparent elastic modulus of bone explants. However, the inhibition of gap junctions or the PGE2 pathway dramatically attenuated the effects of mechanical loading. This 3D trabecular bone explant co-culture model has great potential to fill in the critical gap in knowledge regarding the role of osteocytes as a mechano-sensor and how osteocytes transmit signals to regulate osteoblasts function and skeletal integrity as reflected in its mechanical properties.

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Acknowledgments

We would like to thank Ms. Jiasi Chen for her assistance in histology. This work was supported by NIH grant R21 AR052417 (X. Edward Guo).

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Authors and Affiliations

  1. Bone Bioengineering Laboratory, Department of Biomedical Engineering, Columbia University, 351 Engineering Terrace, Mail Code 8904, 1210 Amsterdam Avenue, New York, NY, 10027, USA

    Meilin Ete Chan, Xin L. Lu, Bo Huo, Andrew D. Baik, Victor Chiang & X. Edward Guo

  2. Institute of Mechanics, Chinese Academy of Sciences, Beijing, 100080, P.R. China

    Bo Huo

  3. Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA, 30332, USA

    Robert E. Guldberg

  4. Biomaterials and Interface Tissue Engineering Laboratory, Department of Biomedical Engineering, Columbia University, New York, NY, 10027, USA

    Helen H. Lu

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  1. Meilin Ete Chan
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Correspondence to X. Edward Guo.

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Chan, M.E., Lu, X.L., Huo, B. et al. A Trabecular Bone Explant Model of Osteocyte–Osteoblast Co-Culture for Bone Mechanobiology. Cel. Mol. Bioeng. 2, 405–415 (2009). https://doi.org/10.1007/s12195-009-0075-5

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