The effect of recombinant human fibroblast growth factor-18 on articular cartilage following single impact load.
Abstract: The aim of this in vitro study was to ascertain the effect of recombinant human Fibroblast Growth Factor-18 (rhFGF18) on the repair response of mechanically damaged articular cartilage. Articular cartilage discs were harvested from healthy mature horses (n = 4) and subjected to single impact load (SIL). The impacted explants, together with unimpacted controls were cultured in modified DMEM ± 200 ng/ml rhFGF18 for up to 30 days. Glycosaminoglycan (GAG) release into the media was measured using the dimethylmethylene blue (DMMB) assay. Aggrecan neopepitope CS846, collagen type II synthesis (CPII) and cleavage (C2C) were measured by ELISA. Histological analysis and TUNEL staining were used to assess repair cell number and cell death. Impacted explants treated with rhFGF18 showed significantly more GAG and CS846 release into the media (p < 0.05), there was also a significant decrease in C2C levels at Day 20. Loaded sections treated with rhFGF18 had more repair cells and significantly less cell death (p < 0.001) at Day 30 in culture. In an in vitro damage/repair model, rhFGF18 increases the proteoglycan synthesis, the repair cell number and prevents apoptosis at Day 30. This suggests that rhFGF18 may be a good candidate for enhancement of cartilage repair following mechanical damage.
© 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.
Publication Date: 2014-04-09 PubMed ID: 24719286DOI: 10.1002/jor.22622Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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This research study explores the effect of a substance known as recombinant human Fibroblast Growth Factor-18 (rhFGF18) on the regeneration of damaged articular cartilage, as seen in conditions such as arthritis. The results indicate that this substance may boost tissue repair, enhancing the presence of helpful cells and key compounds and reducing cell death.
Research Methodology
- The approaching method for this study involved using in vitro, or laboratory, techniques to observe how rhFGF18 affects cartilage repair. Cartilage discs were obtained from healthy adult horses and subjected to a single incident of mechanical load to simulate injury.
- The researchers then cultured these damaged and control cells in a modified version of DMEM (Dulbecco’s Modified Eagle Medium), a nutritional mixture used in biology to support growth in a laboratory environment. These were either combined with rhFGF18, or not, for up to 30 days.
Monitoring Repair Progress
- To track the effectiveness of repair, the team measured Glycosaminoglycan (GAG) release into the culture medium. GAGs are crucial components of cartilage tissue, and increased release usually indicates successful repair.
- Other markers of cartilage health, like the appearance of new Aggrecan epitopes (CS846), and the generation and breakdown of collagen type II (CPII and C2C respectively), were also monitored using an enzyme-linked diagnostic method (ELISA).
- Histological examination (studying the microscopic anatomy of cells and tissues) and TUNEL staining, a technique to measure cell death, were used to calculate repair cell numbers and assess whether there was an increase in cell death.
Results and Significance
- In the case of the damaged samples treated with rhFGF18, there was a significant increase in GAG and CS846 release, indicating successful repair. Additionally, there was a noticeable decrease in the levels of collagen breakdown (C2C levels) by Day 20.
- The study also observed that rhFGF18 treatment resulted in a higher number of repair cells and significantly less cell death by Day 30, suggesting a protective effect.
- The in vitro model suggests that rhFGF18 enhances proteoglycan synthesis (which would support cartilage health), the number of repair cells and prevents apoptosis (cell death) at 30 days, implying that rhFGF18 could be a promising agent for boosting the repair of cartilage after damage.
Cite This Article
APA
Barr L, Getgood A, Guehring H, Rushton N, Henson FM.
(2014).
The effect of recombinant human fibroblast growth factor-18 on articular cartilage following single impact load.
J Orthop Res, 32(7), 923-927.
https://doi.org/10.1002/jor.22622 Publication
Researcher Affiliations
- Orthopaedic Research Unit, Department of Surgery, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 2QQ, United Kingdom.
MeSH Terms
- Aggrecans / metabolism
- Animals
- Apoptosis
- Cartilage, Articular / drug effects
- Cartilage, Articular / injuries
- Cartilage, Articular / metabolism
- Cell Death
- Collagen Type II / metabolism
- Culture Media / chemistry
- Epitopes / metabolism
- Fibroblast Growth Factors / pharmacology
- Glycosaminoglycans / metabolism
- Horses
- Humans
- Recombinant Proteins / pharmacology
- Stress, Mechanical
- Time Factors
- Wound Healing / drug effects
Citations
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