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Cue-Signal-Response Analysis in 3D Chondrocyte Scaffolds with Anabolic Stimuli

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A Correction to this article was published on 06 May 2019

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Abstract

Articular cartilage is an avascular connective tissue responsible for bearing loads. Cell signaling plays a central role in cartilage homeostasis and tissue engineering by directing chondrocytes to synthesize/degrade the extracellular matrix or promote inflammatory responses. The aim of this paper was to investigate anabolic, catabolic and inflammatory pathways of well-known and underreported anabolic stimuli in 3D chondrocyte cultures and connect them to diverse cartilage responses including matrix regeneration and cell communication. A cue-signal-response experiment was performed in chondrocytes embedded in alginate scaffolds subjected to a 9-day treatment with 7 anabolic cues. At the signaling level diverse pathways were measured whereas at the response level glycosaminoglycan (GAG) synthesis and cytokine releases were monitored. A significant increase of GAG was observed for each stimulus and well known anabolic phosphoproteins were activated. In addition, WNK1, an underreported protein of chondrocyte signaling, was uncovered. At the extracellular level, inflammatory and regulating cytokines were measured and DEFB1 and CXCL10 were identified as novel contributors to chondrocyte responses, both closely linked to TLR signaling and inflammation. Finally, two new pro-growth factors with an inflammatory potential, Cadherin-11 and MGP were observed. Interestingly, well-known anabolic stimuli yielded inflammatory responses which pinpoints to the pleiotropic roles of individual stimuli.

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Change history

  • 06 May 2019

    This erratum is to add the following paragraph in the Acknowledgement section:

  • 06 May 2019

    This erratum is to add the following paragraph in the Acknowledgement section:

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None of the authors have any financial interest to disclose.

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Author notes

  1. Michael Neidlin and Antonion Korcari have contributed equally to the work.

Authors and Affiliations

  1. Department of Mechanical Engineering, National Technical University of Athens, Athens, Greece

    Michael Neidlin, Antonion Korcari & Leonidas G. Alexopoulos

  2. 4th Orthopaedic Department, KAT Hospital, Athens, Greece

    Giorgos Macheras

Authors
  1. Michael Neidlin
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  2. Antonion Korcari
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  3. Giorgos Macheras
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  4. Leonidas G. Alexopoulos
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Correspondence to Leonidas G. Alexopoulos.

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Associate Editor Michael S. Detamore oversaw the review of this article.

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Neidlin, M., Korcari, A., Macheras, G. et al. Cue-Signal-Response Analysis in 3D Chondrocyte Scaffolds with Anabolic Stimuli. Ann Biomed Eng 46, 345–353 (2018). https://doi.org/10.1007/s10439-017-1964-8

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  • DOI: https://doi.org/10.1007/s10439-017-1964-8

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