Novel Ex Vivo Human Osteochondral Explant Model of Knee and Spine Osteoarthritis Enables Assessment of Inflammatory and Drug Treatment Responses

Geurts, Jeroen; Jurić, D.; Müller, Monika; Schären, Stefan; Netzer, Cordula

doi:10.3390/ijms19051314

Cited by 36 publications

(37 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Typically, 2D monolayer models involve the culturing of either primary cells or immortalised cell lines Can induce cell de-differentiation, alters cell morphology, cells can become polarised altering their phenotype, has limited potential for investigation into cell-cell and cell-ECM interactions, and has restricted capacity for investigation of loading on tissues [12,25,26,29] Co-culture Facilitates investigation into cell-cell and cell-ECM interactions, allows investigation of the effects of specific compounds on cell phenotypes and interactions, and facilitates investigation into loading regimens on the OA phenotype Requires further refinement of culture conditions, can be costly, cells may de-differentiate depending on co-culture system (i.e. inclusion of a 2D component such as transwell plates) [31,32,36] Explant Considers tissues as a whole, facilitates investigation into cell-cell and cell-ECM interactions, and has potential for co-culture Tissue sources are finite, explants are more financially costly than monolayer models, and cells at surgical edge of tissues may die and influence analysis [33][34][35] Scaffold and scaffold-free systems Maintains cell-differentiated phenotype. Can be highly modifiable.…”

Section: D Cell Modelsmentioning

confidence: 99%

Models of Osteoarthritis: Relevance and New Insights

et al. 2020

View full text Add to dashboard Cite

Osteoarthritis (OA) is a progressive and disabling musculoskeletal disease affecting millions of people and resulting in major healthcare costs worldwide. It is the most common form of arthritis, characterised by degradation of the articular cartilage, formation of osteophytes, subchondral sclerosis, synovial inflammation and ultimate loss of joint function. Understanding the pathogenesis of OA and its multifactorial aetiology will lead to the development of effective treatments, which are currently lacking. Two-dimensional (2D) in vitro tissue models of OA allow affordable, high-throughput analysis and stringent control over specific variables. However, they are linear in fashion and are not representative of physiological conditions. Recent in vitro studies have adopted three-dimensional (3D) tissue models of OA, which retain the advantages of 2D models and are able to mimic physiological conditions, thereby allowing investigation of additional variables including interactions between the cells and their surrounding extracellular matrix. Numerous spontaneous and induced animal models are used to reproduce the onset and monitor the progression of OA based on the aetiology under investigation. This therefore allows elucidation of the pathogenesis of OA and will ultimately enable the development of novel and specific therapeutic interventions. This review summarises the current understanding of in vitro and in vivo OA models in the context of disease pathophysiology, classification and relevance, thus providing new insights and directions for OA research.

show abstract

Section: D Cell Modelsmentioning

confidence: 99%

Models of Osteoarthritis: Relevance and New Insights

et al. 2020

View full text Add to dashboard Cite

show abstract

“…However, changes in the composition and physical properties of the ECM lead to the development of many diseases, including cancer and rheumatic diseases, such as OA and rheumatoid arthritis (RA), among others [5,6]. Moreover, cell stress and ECM degradation promote maladaptive healing reactions, including inflammatory pathways of innate and adaptive immunity [7]. The loss of the biomechanical properties of cartilage induced by prior injuries or increased loading is the most significant feature in the initiation and progression of OA.…”

Section: Introductionmentioning

confidence: 99%

Profile of Matrix-Remodeling Proteinases in Osteoarthritis: Impact of Fibronectin

Pérez‐García

Carrión

Gutiérrez‐Cañas

et al. 2019

Cells

View full text Add to dashboard Cite

The extracellular matrix (ECM) is a complex and specialized three-dimensional macromolecular network, present in nearly all tissues, that also interacts with cell surface receptors on joint resident cells. Changes in the composition and physical properties of the ECM lead to the development of many diseases, including osteoarthritis (OA). OA is a chronic degenerative rheumatic disease characterized by a progressive loss of synovial joint function as a consequence of the degradation of articular cartilage, also associated with alterations in the synovial membrane and subchondral bone. During OA, ECM-degrading enzymes, including urokinase-type plasminogen activator (uPA), matrix metalloproteinases (MMPs), and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTSs), cleave ECM components, such as fibronectin (Fn), generating fibronectin fragments (Fn-fs) with catabolic properties. In turn, Fn-fs promote activation of these proteinases, establishing a degradative and inflammatory feedback loop. Thus, the aim of this review is to update the contribution of ECM-degrading proteinases to the physiopathology of OA as well as their modulation by Fn-fs.

show abstract

“…Osteoarthritis is a disease that is characterized by cartilage degeneration as well as changes in the subchondral bone with a close interrelationship between osteoblasts, osteoclasts, and chondrocytes [94]. Therefore, a clinically relevant preclinical model for osteoarthritis would involve explant tissue consisting of articular cartilage and subchondral bone, the so-called osteochondral unit, which can be obtained from distal femoral condyles or femoral heads [95][96][97]. However, osteochondral cultures were primarily optimized to investigate cartilage regeneration without considering the optimal culture conditions for bone [95,97,98].…”

Section: Ex Vivo Models For Bone Diseasesmentioning

confidence: 99%

Ex vivo Bone Models and Their Potential in Preclinical Evaluation

Cramer

Ito

Hofmann

2021

Curr Osteoporos Rep

View full text Add to dashboard Cite

Purpose of Review Novel therapies for damaged and diseased bone are being developed in a preclinical testing process consisting of in vitro cell experiments followed by in vivo animal studies. The in vitro results are often not representative of the results observed in vivo. This could be caused by the complexity of the natural bone environment that is missing in vitro. Ex vivo bone explant cultures provide a model in which cells are preserved in their native three-dimensional environment. Herein, it is aimed to review the current status of bone explant culture models in relation to their potential in complementing the preclinical evaluation process with specific attention paid to the incorporation of mechanical loading within ex vivo culture systems. Recent Findings Bone explant cultures are often performed with physiologically less relevant bone, immature bone, and explants derived from rodents, which complicates translatability into clinical practice. Mature bone explants encounter difficulties with maintaining viability, especially in static culture. The integration of mechanical stimuli was able to extend the lifespan of explants and to induce new bone formation. Summary Bone explant cultures provide unique platforms for bone research and mechanical loading was demonstrated to be an important component in achieving osteogenesis ex vivo. However, more research is needed to establish a representative, reliable, and reproducible bone explant culture system that includes both components of bone remodeling, i.e., formation and resorption, in order to bridge the gap between in vitro and in vivo research in preclinical testing.

show abstract

Novel Ex Vivo Human Osteochondral Explant Model of Knee and Spine Osteoarthritis Enables Assessment of Inflammatory and Drug Treatment Responses

Cited by 36 publications

References 39 publications

Models of Osteoarthritis: Relevance and New Insights

Models of Osteoarthritis: Relevance and New Insights

Profile of Matrix-Remodeling Proteinases in Osteoarthritis: Impact of Fibronectin

Ex vivo Bone Models and Their Potential in Preclinical Evaluation

Contact Info

Product

Resources

About