The Releasate of Avascular Cartilage Demonstrates Inherent Pro-Angiogenic Properties In Vitro and In Vivo

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Objective. Cartilage is avascular and numerous studies have identified the presence of single anti- and pro-angiogenic
factors in cartilage. To better understand the maintenance hyaline cartilage, we assessed the angiogenic potential of
complete cartilage releasate with functional assays in vitro and in vivo. Design. We evaluated the gene expression profile
of angiogenesis-related factors in healthy adult human articular cartilage with a transcriptome-wide analysis generated
by next-generation RNAseq. The effect on angiogenesis of the releasate of cartilage tissue was assessed with a chick
chorioallantoic membrane (CAM) assay as well as human umbilical vein endothelial cell (HUVEC) migration and
proliferation assays using conditioned media generated from tissue-engineered cartilage derived from human articular
and nasal septum chondrocytes as well as explants from bovine articular cartilage and human nasal septum. Experiments
were done with triplicate samples of cartilage from 3 different donors. Results. RNAseq data of 3 healthy human articular
cartilage donors revealed that the majority of known angiogenesis-related factors expressed in healthy adult articular
cartilage are pro-angiogenic. The releasate from generated cartilage as well as from tissue explants, demonstrated at
least a 3.1-fold increase in HUVEC proliferation and migration indicating a pro-angiogenic effect of cartilage. Finally, the
CAM assay demonstrated that cartilage explants can indeed attract vessels; however, their ingrowth was not observed.
Conclusion. Using multiple approaches, we show that cartilage releasate has an inherent pro-angiogenic capacity. It remains
vessel free due to anti-invasive properties associated with the tissue itself.
Original languageEnglish
Pages (from-to)559S–570S
Number of pages12
Issue number2
Early online date30 Sep 2021
Publication statusPublished - 2021

Bibliographical note

Acknowledgments and Funding
This work was performed within the framework of the Erasmus Postgraduate School Molecular Medicine and Medical Delta Regenerative Medicine 4D program. The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This project has received funding from the European Union’s Horizon 2020 research and innovation program under Marie Sklodowska-Curie grant agreement no. 721432. This project has received funding from NIH/NIBIB: 1P41EB021911 “CWRU Center for Multimodal Evaluation of Engineered Cartilage”.


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