This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Research article
Ernst Bruno Hunziker
Inselspital Universitatsspital Bern
Corresponding Author
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The autologous synovium is a potential tissue source for local induction of chondrogenesis by tissue engineering approaches to repair articular cartilage defects such as they occur in osteoarthritis. It was the aim of the present study to ascertain whether the aging of osteoarthritic patients compromises the chondrogenic potential of their knee-joint synovium.
The patients were allocated to one of the following two age categories: 54 - 65 years and 66 - 86 years (n = 7-11 donors per time point and per experimental group). Synovial biopsies were induced in vitro to undergo chondrogenesis by exposing them to either bone morphogenetic protein-2 (BMP-2) alone, transforming growth factor-ß1 (TGF-ß1) alone, or a combination of the two growth factors for up to 6 weeks. The differentiated explants were evaluated histomorphometrically for the volume fraction of metachromasia (sulfated proteoglycans), immunohistochemically for type-II collagen, and for the gene-expression levels of anabolic chondrogenic markers as well as catabolic factors by a real-time polymerase-chain-reaction (RT-PCR) analysis.
Quantitative metachromasia revealed that chondrogenic differentiation of human synovial explants was induced to the greatest degree by either BMP-2 alone or the BMP-2/TGF-b1 combination, i.e. to a comparable level with each of the two stimulation protocols and within both age categories. The gene-expression levels of the anabolic chondrogenic markers confirmed the superiority of these two stimulation protocols and demonstrated the hyaline-like qualities of the generated cartilaginous matrix. The gene-expression levels of the catabolic markers were extremely low.
Our data reveal the chondrogenic potential of the human knee-joint synovium of osteoarthritic patients to be uncompromised by ageing and catabolic processes. The potential of synovium-based clinical engineering (repair) of cartilage tissue using autologous synovium may thus not be reduced by the age of the human patient.
Keywords
Synovium, osteoarthritis, age, chondrogenesis, BMP-2, TGF-β1
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This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Research article
Ernst Bruno Hunziker
Inselspital Universitatsspital Bern
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
Version 1
Posted 04 Feb, 2021
No community comments so far
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Orthopedics
License:
This work is licensed under a CC BY 4.0 License. Read Full License
The autologous synovium is a potential tissue source for local induction of chondrogenesis by tissue engineering approaches to repair articular cartilage defects such as they occur in osteoarthritis. It was the aim of the present study to ascertain whether the aging of osteoarthritic patients compromises the chondrogenic potential of their knee-joint synovium.
The patients were allocated to one of the following two age categories: 54 - 65 years and 66 - 86 years (n = 7-11 donors per time point and per experimental group). Synovial biopsies were induced in vitro to undergo chondrogenesis by exposing them to either bone morphogenetic protein-2 (BMP-2) alone, transforming growth factor-ß1 (TGF-ß1) alone, or a combination of the two growth factors for up to 6 weeks. The differentiated explants were evaluated histomorphometrically for the volume fraction of metachromasia (sulfated proteoglycans), immunohistochemically for type-II collagen, and for the gene-expression levels of anabolic chondrogenic markers as well as catabolic factors by a real-time polymerase-chain-reaction (RT-PCR) analysis.
Quantitative metachromasia revealed that chondrogenic differentiation of human synovial explants was induced to the greatest degree by either BMP-2 alone or the BMP-2/TGF-b1 combination, i.e. to a comparable level with each of the two stimulation protocols and within both age categories. The gene-expression levels of the anabolic chondrogenic markers confirmed the superiority of these two stimulation protocols and demonstrated the hyaline-like qualities of the generated cartilaginous matrix. The gene-expression levels of the catabolic markers were extremely low.
Our data reveal the chondrogenic potential of the human knee-joint synovium of osteoarthritic patients to be uncompromised by ageing and catabolic processes. The potential of synovium-based clinical engineering (repair) of cartilage tissue using autologous synovium may thus not be reduced by the age of the human patient.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
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