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Updated: Jun 12, 2026

Establishment and Evaluation of a Sheep Model of Full-thickness Osteochondral Defect
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Engineered Chondrocalcin From Pichia pastoris: A Dual-Functional Biomaterial for Cartilage Regeneration and

Wensha Zhu1,2,3, Zilong Zhao1,2,3, Weigang Yuwen2

  • 1School of Chemical Engineering, Engineering Research Center of Western Resource Innovation Medicine Green Manufacturing, Ministry of Education, Northwest University, Xi'an, China.

Biotechnology and Bioengineering
|June 11, 2026
PubMed
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Recombinant chondrocalcin (rCCN) promotes cartilage repair by enhancing bone marrow mesenchymal stem cell differentiation and reprogramming inflammatory environments in rheumatoid arthritis. This peptide shows dual therapeutic potential for cartilage regeneration and inflammation modulation.

Area of Science:

  • Biomaterials Science
  • Cell Biology
  • Rheumatology

Background:

  • Chondrocalcin (CCN), a key peptide in collagen assembly, is crucial for cartilage health.
  • Dysregulation of CCN is linked to bone-cartilage interface disorders.
  • Developing effective cartilage repair strategies and anti-inflammatory treatments remains a challenge.

Purpose of the Study:

  • To engineer and characterize recombinant chondrocalcin (rCCN) for therapeutic applications.
  • To investigate the potential of rCCN in promoting chondrogenesis in human bone marrow mesenchymal stem cells (hBMSCs).
  • To evaluate the immunomodulatory effects of rCCN in rheumatoid arthritis synoviocytes (HFLS-RA).

Main Methods:

  • Genetic engineering of Pichia pastoris to produce rCCN.
Keywords:
anti‐inflammatorybiomaterialcartilage regenerationchondrocalcin

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  • Isolation, purification, and characterization of rCCN.
  • In vitro functional assays using hBMSCs and HFLS-RA cells to assess chondrogenesis and inflammatory responses.

    • Main Results:

    • rCCN significantly promoted hBMSC differentiation into chondrocytes.
    • rCCN upregulated key chondrogenic markers (SOX9, COLII, aggrecan) and suppressed fibrotic COL I.
    • rCCN modulated the inflammatory microenvironment in HFLS-RA cells by upregulating COLII, IL-4, and TGF-β1, while downregulating TNF-α, IL-1β, and IL-6.

    Conclusions:

    • rCCN demonstrates significant potential for cartilage regeneration by enhancing chondrogenesis.
    • rCCN exhibits potent anti-inflammatory properties, suggesting its utility in managing inflammatory joint diseases.
    • rCCN presents a dual therapeutic approach for cartilage repair and inflammatory modulation in joint disorders.