Validation of an in vitro single-impact load model of the initiation of osteoarthritis-like changes in articular cartilage.
Abstract: The objective of this study was the development and characterization of an in vitro model of the initiation of traumatic osteoarthritis (OA). Articular cartilage was obtained from seven healthy horses and from four horses diagnosed with OA. Cartilage disks were subjected to a single-impact load (500 g from 25, 50, or 100 mm) using a simple drop-tower device and cultured in vitro for up to 20 days. Cartilage sections were examined histologically to observe surface damage and proteoglycan loss. Percentage cell death was determined using TUNEL, release of glycosaminoglycans (GAG) to the medium was measured using the DMMB assay, and percentage weight gain calculated. Following a single-impact load and subsequent culture in vitro, articular cartilage explants demonstrated characteristic surface damage, proteoglycan loss, and chondrocyte death. This closely resembled degenerative changes observed in OA cartilage samples. A kinetic study showed that these degenerative changes (increased weight gain, GAG release into the medium, and chondrocyte death) were initiated within 48 h following impact and increased with recovery time in culture. These parameters were proportional to impact height, that is, impact energy. In conclusion, articular cartilage disks subjected to a single-impact load followed by 48 h of recovery time in culture in vitro developed traumatic OA-like changes. These changes can be quantified and compared, making the in vitro single-impact load model a useful tool for the elucidation of the early molecular pathways involved in the process leading from trauma to cartilage degeneration.
Copyright 2006 Orthopaedic Research Society
Publication Date: 2006-03-04 PubMed ID: 16514652DOI: 10.1002/jor.20111Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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This research article focuses on developing and characterizing an in vitro model for initiating traumatic osteoarthritis (OA) using articular cartilage. The outcomes show that cartilage samples subjected to a single impact load followed by a 48-hour recovery period developed degenerative changes similar to those observed in OA cases.
Methodology
- In this experiment, the researchers collected articular cartilage from 7 healthy horses and 4 horses diagnosed with OA to investigate the initiation of the degenerative disease.
- The acquired cartilage discs were subjected to a single-impact load, with varying weight intensities (500 g, dropped from 25, 50, or 100 mm heights), using a basic drop-tower device.
- Post impact, the cartilage discs were cultured in vitro (outside the body) for a period of up to 20 days.
Multiple Analysis Techniques
- Following the culture period, the cartilage sections were examined histologically to observe the level of surface damage and the loss of proteoglycan – a protein that plays a critical role in maintaining the structural integrity of cartilage.
- The percentage of cell death was determined using TUNEL, a method that specifically detects fragmented DNA of dying cells.
- The release of glycosaminoglycans (GAG), which are a component of proteoglycans, into the medium during the culture period was quantified using the DMMB assay.
- The percentage weight gain of the cartilage discs was also calculated to evaluate the changes post traumatic impact.
Findings
- It was observed that the articular cartilage explants exhibited characteristic surface damage, proteoglycan loss, and chondrocyte (cells found in cartilage) death, mimicking the degenerative changes observed in OA cartilage samples.
- The changes such as increase in weight gain, release of GAG into the medium, and chondrocyte death were initiated within 48 hours following the impact and increased with the recovery period in the culture.
- All these parameters were proportional to the impact energy, i.e., the height from which the weight was dropped.
Conclusions
- The study concluded that articular cartilage discs that are subjected to a single-impact load and cultured in vitro for 48 hours develop changes that resemble the onset of traumatic OA.
- Moreover, these changes can be quantified and compared, thus proving that the in vitro single-impact load model can be effectively used to unravel early molecular pathways that lead from trauma to cartilage degeneration, a characteristic of OA.
Cite This Article
APA
Huser CA, Davies ME.
(2006).
Validation of an in vitro single-impact load model of the initiation of osteoarthritis-like changes in articular cartilage.
J Orthop Res, 24(4), 725-732.
https://doi.org/10.1002/jor.20111 Publication
Researcher Affiliations
- Comparative Orthopaedics Research Group, Department of Veterinary Medicine, University of Cambridge, Cambridge, CB3 0ES, United Kingdom. ch353@cam.ac.uk
MeSH Terms
- Animals
- Apoptosis
- Cartilage, Articular / pathology
- Chondrocytes / pathology
- Collagen Type II / analysis
- Disease Models, Animal
- Horses
- In Situ Nick-End Labeling
- Osteoarthritis / pathology
- Proteoglycans / metabolism
- Weight Gain
Citations
This article has been cited 17 times.- Jones RC, Lawrence KM, Higgins SM, Richardson SM, Townsend PA. Urocortin-1 Is Chondroprotective in Response to Acute Cartilage Injury via Modulation of Piezo1.. Int J Mol Sci 2022 May 4;23(9).
- Huppertz MS, Schock J, Radke KL, Abrar DB, Post M, Kuhl C, Truhn D, Nebelung S. Longitudinal T2 Mapping and Texture Feature Analysis in the Detection and Monitoring of Experimental Post-Traumatic Cartilage Degeneration.. Life (Basel) 2021 Mar 5;11(3).
- Costello KE, Felson DT, Neogi T, Segal NA, Lewis CE, Gross KD, Nevitt MC, Lewis CL, Kumar D. Ground reaction force patterns in knees with and without radiographic osteoarthritis and pain: descriptive analyses of a large cohort (the Multicenter Osteoarthritis Study).. Osteoarthritis Cartilage 2021 Aug;29(8):1138-1146.
- Haltmayer E, Ribitsch I, Gabner S, Rosser J, Gueltekin S, Peham J, Giese U, Dolezal M, Egerbacher M, Jenner F. Co-culture of osteochondral explants and synovial membrane as in vitro model for osteoarthritis.. PLoS One 2019;14(4):e0214709.
- Nickien M, Heuijerjans A, Ito K, van Donkelaar CC. Comparison between in vitro and in vivo cartilage overloading studies based on a systematic literature review.. J Orthop Res 2018 Apr 12;36(8):2076-86.
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- Bartell LR, Fortier LA, Bonassar LJ, Cohen I. Measuring microscale strain fields in articular cartilage during rapid impact reveals thresholds for chondrocyte death and a protective role for the superficial layer.. J Biomech 2015 Sep 18;48(12):3440-6.
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- Olson SA, Furman BD, Kraus VB, Huebner JL, Guilak F. Therapeutic opportunities to prevent post-traumatic arthritis: Lessons from the natural history of arthritis after articular fracture.. J Orthop Res 2015 Sep;33(9):1266-77.
- Onur TS, Wu R, Chu S, Chang W, Kim HT, Dang AB. Joint instability and cartilage compression in a mouse model of posttraumatic osteoarthritis.. J Orthop Res 2014 Feb;32(2):318-23.
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