Promotion of the intrinsic damage-repair response in articular cartilage by fibroblastic growth factor-2.
Abstract: To identify the effect of fibroblastic growth factor-2 (FGF-2) on the intrinsic damage-repair response in articular cartilage in vitro. Methods: Articular equine cartilage explants, without subchondral bone, had a single impact load of 500 g applied from a height of 2.5 cm. Explants were then cultured in 0, 12, 25, 50 or 100 ng/ml FGF-2 for up to 28 days. Unimpacted discs served as controls for each time-point. Histological and immunohistochemical techniques were used to quantify and characterise the response of putative chondrocyte progenitor cells (CPC) to damage and FGF-2 treatment. Results: FGF-2 significantly accelerated the appearance and increased the numbers of de novo repair cells identified histologically at the cartilage surface. The response was affected by the dose of FGF-2. The repair cells were shown to be chondrocytes by their expression of collagen types II, IX/XI, but not of type I collagen. In addition, these cells, and those underlying the articular surface, were shown to be immunopositive for Notch-1 and PCNA, markers for proliferating cartilage progenitor cells. Conclusions: The results of this study indicate that, following single impact load, CPC can be stimulated in mature articular cartilage in vitro. These CPC and the cells arising from them appear to represent the cartilage's response to damage. The timing of the appearance of CPC and their overall numbers can be significantly increased by FGF-2, providing further evidence for an important role for FGF-2 in modulating cartilage repair. These results indicate that further study into the mechanisms of repair in mature cartilage using this in vitro model are vital in understanding the repair capacity of mature cartilage.
Publication Date: 2005-06-01 PubMed ID: 15922188DOI: 10.1016/j.joca.2005.02.007Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The research seeks to understand the role of fibroblastic growth factor-2 (FGF-2) in repairing damaged articular cartilage. It demonstrates that FGF-2 can hasten the appearance and increase the number of repair cells in the cartilage.
Methodology
- The researchers isolated articular cartilage from horses, and inflicted impact damage on it by dropping a 500g weight from a height of 2.5cm.
- The damaged cartilage samples were then cultured in varying concentrations of FGF-2 (ranging from 0 to 100 ng/ml) for a duration of up to 28 days.
- Undamaged cartilage samples were also cultured under similar conditions for comparison.
- Using histological and immunohistochemical techniques, the team tracked the response of chondrocyte progenitor cells (CPC) – the cells responsible for the repair of cartilage – to the damage and FGF-2 treatment.
Results
- The study discovered that FGF-2 considerably fastened the appearance and ramped up the numbers of repair cells that could be visually identified on the cartilage surface.
- This response was found to be dose-dependent, with higher doses of FGF-2 leading to a stronger reaction.
- The repair cells were confirmed as chondrocytes due to their production of collagen types II, IX/XI, but not I.
- These cells also tested positive for Notch-1 and PCNA, both markers for proliferating cartilage progenitor cells.
Conclusions
- The results showed that CPCs can be stimulated in adult articular cartilage in a controlled environment, post-impact.
- These stimulated CPCs and the resulting cells seem to signify the cartilage’s intrinsic method to combat damage.
- The timing of CPC appearance, along with their final count, can be significantly boosted by FGF-2. This lends further proof to FGF-2’s vital role in steering cartilage repair.
- The outcomes propose that exploring the mechanisms of repair in mature cartilage using this controlled model could be essential in understanding the repair capacity of aged cartilage.
Cite This Article
APA
Henson FM, Bowe EA, Davies ME.
(2005).
Promotion of the intrinsic damage-repair response in articular cartilage by fibroblastic growth factor-2.
Osteoarthritis Cartilage, 13(6), 537-544.
https://doi.org/10.1016/j.joca.2005.02.007 Publication
Researcher Affiliations
- Department of Clinical Veterinary Medicine, University of Cambridge, Madingley Road, Cambridge CB3 0ES, UK. fmdh1@cam.ac.uk
MeSH Terms
- Animals
- Cartilage, Articular / drug effects
- Cartilage, Articular / injuries
- Cartilage, Articular / pathology
- Chondrogenesis / drug effects
- Equidae
- Fibroblast Growth Factor 2 / pharmacology
- In Vitro Techniques
- Stem Cells / drug effects
- Wound Healing / drug effects
Citations
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