Comparison between in vitro and in vivo cartilage overloading studies based on a systematic literature review

Abstract

Methodological differences between in vitro and in vivo studies on cartilage overloading complicate the comparison of outcomes. The rationale of the current review was to (i) identify consistencies and inconsistencies between in vitro and in vivo studies on mechanically‐induced structural damage in articular cartilage, such that variables worth interesting to further explore using either one of these approaches can be identified; and (ii) suggest how the methodologies of both approaches may be adjusted to facilitate easier comparison and therewith stimulate translation of results between in vivo and in vitro studies. This study is anticipated to enhance our understanding of the development of osteoarthritis, and to reduce the number of in vivo studies. Generally, results of in vitro and in vivo studies are not contradicting. Both show subchondral bone damage and intact cartilage above a threshold value of impact energy. At lower loading rates, excessive loads may cause cartilage fissuring, decreased cell viability, collagen network de‐structuring, decreased GAG content, an overall damage increase over time, and low ability to recover. This encourages further improvement of in vitro systems, to replace, reduce, and/or refine in vivo studies. However, differences in experimental set up and analyses complicate comparison of results. Ways to bridge the gap include (i) bringing in vitro set‐ups closer to in vivo, for example, by aligning loading protocols and overlapping experimental timeframes; (ii) synchronizing analytical methods; and (iii) using computational models to translate conclusions from in vitro results to the in vivo environment and vice versa. © 2018 The Authors. Journal of Orthopaedic Research® Published by Wiley Periodicals, Inc. on behalf of the Orthopaedic Research Society. J Orthop Res 36:2076–2086, 2018.

An Evidence-Based Systematic Review of Human Knee Post-Traumatic Osteoarthritis (PTOA): Timeline of Clinical Presentation and Disease Markers, Comparison of Knee Joint PTOA Models and Early Disease Implications

“…Other reviews [ 139 , 140 ] have well described how articular cartilage explant models have used various types of injurious compression protocols to simulate mechanical injury and have demonstrated that, despite differences in protocols, these models show that they similarly and successfully induce the clinically observed pathologies following trauma to the knee joint. Hence, the mechanically-induced injury of articular cartilage leads to a significant increase in chondrocyte death, ECM loss, expression of matrix-degrading enzymes and a decrease in the COL2 gene and, to some extent, an increase in inflammatory cytokines even in the absence of inflammatory cells, such as macrophages [ 141 , 142 , 143 , 144 , 145 , 146 , 147 , 148 , 149 , 150 , 151 , 152 , 153 ].…”

The Dysregulated Galectin Network Activates NF-κB to Induce Disease Markers and Matrix Degeneration in 3D Pellet Cultures of Osteoarthritic Chondrocytes

“…This justifies vigorous efforts to systematically study the molecular basis of disease onset and progression with the aim to develop innovative therapeutic strategies that interfere with the complex OA pathogenesis [ 2 , 3 ], currently culminating in multi-omics approaches to identify relevant molecular signatures [ 4 ]. Obviously, the strategic combination of work on clinical material with tailored in vitro models would be helpful to generate meaningful pathobiological results and improve translatability of new knowledge into clinical practice [ 5 ]. From a practical perspective, two-dimensional (2D) cell cultures have been considered as the starting point on the way to mimic an in situ-like microenvironment in vitro .…”

A Post‐Traumatic Osteoarthritic Model of Hip Following Fracture of Acetabulum in Rabbit: A Preliminary Study by Macroscopic and Radiographic Assessment

“…There are several limitations to the present study. First, in addition to the magnitude of load, injuries would also be affected by loading rate 31–33 , which cannot be separated in the present drop‐tower impacting configuration. Therefore, the rabbit model cannot completely simulate motor vehicle dashboard‐type injury.…”