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

Takashi Iwakura, Atsuyuki Inui, A Hari Reddi

Research output: Contribution to journalArticle

10 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)408-417
Number of pages10
JournalArthritis and Rheumatism
Issue number2
StatePublished - Feb 2013


ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Rheumatology
  • Pharmacology (medical)

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