Cartilage type IIB procollagen NH<sub>2</sub>-propeptide, PIIBNP, inhibits angiogenesis

Zhepeng Wang; Aiwu Lu; Zhepeng Wang; Aiwu Lu

doi:10.3934/molsci.2021022

AIMS Molecular Science

2021, Volume 8, Issue 4: 291-300. doi: 10.3934/molsci.2021022

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Research article

Cartilage type IIB procollagen NH₂-propeptide, PIIBNP, inhibits angiogenesis

Zhepeng Wang ^{1
,
,},
Aiwu Lu ²

1.
Department of Anesthesiology, University of Massachusetts Chan Medical School, 55 N. Lake Avenue, Worcester, MA 01655, USA
2.
Department of Orthopaedic Surgery, Washington University School of Medicine, USA

Received: 02 November 2021 Accepted: 15 December 2021 Published: 23 December 2021

Cartilage tissue is avascular and resistant to tumor invasion, but the basis for these properties is still unclear. Here we report that the NH₂-propeptide of type IIB procollagen (PIIBNP), a product of collagen biosynthesis, is capable of inhibiting angiogenesis both in vitro and in vivo. PIIBNP inhibits tube formation in human umbilical vein cells (HUVEC), inhibits endogenous endothelial cell outgrowth in mouse aortic ring angiogenesis bioassay and is anti-angiogenic in the mouse cornea angiogenesis assay. As α_Vß₃ and α_Vß₅ integrins are expressed primarily in endothelial cells, cancer cells and osteoclasts, but not in normal chondrocytes and PIIBNP binds to cell surface integrin α_Vß₃ and αVß₅, we propose that natural occurring PIIBNP protects cartilage by targeting endothelial cells during chondrogenesis, thus inhibiting angiogenesis, and rendering the tissue avascular.
- cartilage,
- NH2-propeptide,
- avascularity,
- angiogenesis,
- inhibitor
Citation: Zhepeng Wang, Aiwu Lu. Cartilage type IIB procollagen NH2-propeptide, PIIBNP, inhibits angiogenesis[J]. AIMS Molecular Science, 2021, 8(4): 291-300. doi: 10.3934/molsci.2021022

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Abstract

Cartilage tissue is avascular and resistant to tumor invasion, but the basis for these properties is still unclear. Here we report that the NH₂-propeptide of type IIB procollagen (PIIBNP), a product of collagen biosynthesis, is capable of inhibiting angiogenesis both in vitro and in vivo. PIIBNP inhibits tube formation in human umbilical vein cells (HUVEC), inhibits endogenous endothelial cell outgrowth in mouse aortic ring angiogenesis bioassay and is anti-angiogenic in the mouse cornea angiogenesis assay. As α_Vß₃ and α_Vß₅ integrins are expressed primarily in endothelial cells, cancer cells and osteoclasts, but not in normal chondrocytes and PIIBNP binds to cell surface integrin α_Vß₃ and αVß₅, we propose that natural occurring PIIBNP protects cartilage by targeting endothelial cells during chondrogenesis, thus inhibiting angiogenesis, and rendering the tissue avascular.

Acknowledgments

We thank for Dr. William Frazier (Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine) for generous gifts of HUVEC cells and Brian J. Ell (Pathology, University of Wisconsin) for help in mouse corneal angiogenesis assays.

Conflict of interest

The authors declare no conflict of interest.

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