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Osteoarthritis and cartilage2010; 18(11); 1477-1486; doi: 10.1016/j.joca.2010.07.015

Adult bone marrow stromal cell-based tissue-engineered aggrecan exhibits ultrastructure and nanomechanical properties superior to native cartilage.

Abstract: To quantify the structural characteristics and nanomechanical properties of aggrecan produced by adult bone marrow stromal cells (BMSCs) in peptide hydrogel scaffolds and compare to aggrecan from adult articular cartilage. Methods: Adult equine BMSCs were encapsulated in 3D-peptide hydrogels and cultured for 21 days with TGF-β1 to induce chondrogenic differentiation. BMSC-aggrecan was extracted and compared with aggrecan from age-matched adult equine articular cartilage. Single molecules of aggrecan were visualized by atomic force microscopy-based imaging and aggrecan nanomechanical stiffness was quantified by high resolution force microscopy. Population-averaged measures of aggrecan hydrodynamic size, core protein structures and CS sulfation compositions were determined by size-exclusion chromatography, Western analysis, and fluorescence-assisted carbohydrate electrophoresis (FACE). Results: BMSC-aggrecan was primarily full-length while cartilage-aggrecan had many fragments. Single molecule measurements showed that core protein and GAG chains of BMSC-aggrecan were markedly longer than those of cartilage-aggrecan. Comparing full-length aggrecan of both species, BMSC-aggrecan had longer GAG chains, while the core protein trace lengths were similar. FACE analysis detected a ∼ 1:1 ratio of chondroitin-4-sulfate to chondroitin-6-sulfate in BMSC-GAG, a phenotype consistent with aggrecan from skeletally-immature cartilage. The nanomechanical stiffness of BMSC-aggrecan was demonstrably greater than that of cartilage-aggrecan at the same total sGAG (fixed charge) density. Conclusions: The higher proportion of full-length monomers, longer GAG chains and greater stiffness of the BMSC-aggrecan makes it biomechanically superior to adult cartilage-aggrecan. Aggrecan stiffness was not solely dependent on fixed charge density, but also on GAG molecular ultrastructure. These results support the use of adult BMSCs for cell-based cartilage repair.
Copyright © 2010 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
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Publication Date: 2010-08-06 PubMed ID: 20692354PubMed Central: PMC2975943DOI: 10.1016/j.joca.2010.07.015Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The study aims to compare the structural characteristics and nanomechanical properties of aggrecan synthesized by adult bone marrow stromal cells (BMSCs) in a laboratory setting with those of aggrecan present in adult articular cartilage. The observed findings highlight the enhanced biomechanical properties of BMSC-produced aggrecan, supporting its potential use in cartilage repair efforts.

Study Design and Methods

  • The research utilized adult equine BMSCs, which were enclosed in 3D-peptide hydrogels and then cultured for 21 days with a substance called TGF-β1 to stimulate the differentiation of these cells into chondrocytes – cells that produce and maintain the extracellular matrix of cartilage.
  • The scientists extracted the aggrecan synthesized by these BMSCs and compared its structure and properties with those of aggrecan derived from adult equine articular cartilage from age-matched specimens.
  • Aggrecan molecules were imaged using atomic force microscopy and their nanomechanical stiffness was quantified by high-resolution force microscopy. Additionally, the average measures of aggrecan hydrodynamic size, core protein structures and CS sulfation compositions were evaluated through size-exclusion chromatography, Western analysis, and a technique called fluorescence-assisted carbohydrate electrophoresis (FACE).

Results

  • The aggrecan produced by adult BMSCs was mostly full-length, whereas the carilage-derived aggrecan contained many shortened, fragmented molecules.
  • Single molecule measurements showed that the core protein and the glycosaminoglycan (GAG) chains of BMSC-produced aggrecan were significantly longer than those of cartilage-aggrecan.
  • The FACE analysis revealed a roughly 1:1 ratio of two variants of chondroitin sulfate – chondroitin-4-sulfate to chondroitin-6-sulfate – in BMSC-derived GAG, an observation that aligns with aggrecan from skeletally-immature cartilage.
  • The BMSC-aggrecan was found to be mechanically stiffer than cartilage-aggrecan at an equivalent fixed charge density, suggesting that this stiffness is not merely dependent on charge density, but also on the molecular ultrastructure of GAG.

Conclusions

  • The results showed that aggrecan from BMSCs, due to its higher portion of full-length monomers, longer GAG chains, and superior stiffness, was biomechanically superior to aggrecan derived from adult cartilage.
  • These findings endorse the potential use of adult BMSCs in procedures aimed at repairing cartilage, as these cells have been shown capable of producing a superior extracellular matrix component.
  • The study also adds to our understanding of the molecular mechanisms contributing to the mechanical properties of aggrecan, emphasizing the role of GAG molecular ultrastructure in addition to charge density.

Cite This Article

APA
Lee HY, Kopesky PW, Plaas A, Sandy J, Kisiday J, Frisbie D, Grodzinsky AJ, Ortiz C. (2010). Adult bone marrow stromal cell-based tissue-engineered aggrecan exhibits ultrastructure and nanomechanical properties superior to native cartilage. Osteoarthritis Cartilage, 18(11), 1477-1486. https://doi.org/10.1016/j.joca.2010.07.015

Publication

Osteoarthritis and cartilage
ISSN: 1522-9653
NlmUniqueID: 9305697
Country: England
Language: English
Volume: 18
Issue: 11
Pages: 1477-1486

Researcher Affiliations

Lee, H-Y
  • Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, MA, USA.
Kopesky, P W
    Plaas, A
      Sandy, J
        Kisiday, J
          Frisbie, D
            Grodzinsky, A J
              Ortiz, C

                MeSH Terms

                • Aggrecans / biosynthesis
                • Aggrecans / chemistry
                • Aggrecans / ultrastructure
                • Animals
                • Biomechanical Phenomena
                • Blotting, Western
                • Bone Marrow Cells / cytology
                • Cartilage, Articular / chemistry
                • Cartilage, Articular / ultrastructure
                • Electrophoresis / methods
                • Glycosaminoglycans / chemistry
                • Glycosaminoglycans / ultrastructure
                • Horses
                • Microscopy, Atomic Force
                • Nanotechnology
                • Stromal Cells / cytology
                • Tissue Engineering / methods

                Grant Funding

                • R01 AR033236 / NIAMS NIH HHS
                • R37 AR033236 / NIAMS NIH HHS
                • R01 EB003805 / NIBIB NIH HHS
                • EB003805 / NIBIB NIH HHS
                • AR33236 / NIAMS NIH HHS

                Conflict of Interest Statement

                All the authors have no financial and personal relation ships with other people or organizations that could potentially and inappropriately influence their work and conclusions.

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