Stimulation of superficial zone protein accumulation by hedgehog and Wnt signaling in surface zone bovine articular chondrocytes

Authors

  • Takashi Iwakura,

    Corresponding author
    1. Center for Tissue Regeneration and Repair, University of California, Davis
    • Center for Tissue Regeneration and Repair, Department of Orthopaedic Surgery, University of California, Davis, 4635 Second Avenue, Research Building I, Room 2000, Sacramento, CA 95817
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  • Atsuyuki Inui,

    1. Center for Tissue Regeneration and Repair, University of California, Davis
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  • A. Hari Reddi

    Corresponding author
    1. Center for Tissue Regeneration and Repair, University of California, Davis
    • Center for Tissue Regeneration and Repair, Department of Orthopaedic Surgery, University of California, Davis, 4635 Second Avenue, Research Building I, Room 2000, Sacramento, CA 95817
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Abstract

Objective

To determine the roles of the hedgehog and Wnt signaling pathways in accumulation of superficial zone protein (SZP) in surface zone articular chondrocytes.

Methods

Explant cultures of disks of surface zone cartilage or isolated chondrocytes from the surface zone of articular cartilage of bovine stifle joints were cultured in serum-free chemically defined medium. Accumulation of SZP in the culture medium, in response to hedgehog proteins (sonic hedgehog [SHH] and Indian hedgehog [IHH]), Wnt proteins (Wnt-3a, Wnt-5a, and Wnt-11), agonists of the Wnt/β-catenin pathway (glycogen synthase kinase 3β [GSK-3β] inhibitors), and antagonists of the Wnt/β-catenin pathway, was investigated. The interaction between transforming growth factor β1 (TGFβ1) and hedgehog proteins or antagonists of the Wnt/β-catenin pathway was also investigated.

Results

Hedgehog proteins stimulated SZP accumulation. Activation of the Wnt/β-catenin pathway by Wnt-3a and GSK-3β inhibitors led to inhibition of SZP accumulation; however, Wnt-5a and Wnt-11 had no influence on SZP accumulation. Conversely, antagonists of the Wnt/β-catenin pathway stimulated SZP accumulation. In addition, there were combinatorial effects of TGFβ1 and hedgehog proteins or antagonists of the Wnt/β-catenin pathway on SZP accumulation.

Conclusion

SHH and IHH signaling has a stimulatory effect on SZP accumulation in surface zone cartilage and isolated articular chondrocytes. These findings provide insight into the regulatory mechanisms of articular cartilage homeostasis and maintenance by morphogens.

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