Mechanical loading is an essential part of the function and maintenance of the joint. Despite the importance of intermittent mechanical loading, this factor is rarely considered in preclinical models of cartilage, limiting their translatability.
The cartilage of the joints of patients with osteoarthritis is negatively affected in their capacity to absorb the load. Despite this pivotal role, mechanical load is rarely a component of translational drug screening assays when testing novel OA treatments.
We showcased our novel translational cartilage loading model in a publication in Applied Sciences.
Cartilage explant isolation
In a culture plate format well suited for lead candidate screening we investigated the effect of growth factors on ex-vivo cartilage remodeling and the interaction with dynamic intermittent loading. Cartilage remodeling was investigated in the presence of IGF-1 or TGF-β1, as well as a TGF-β receptor 1 (ALK5) kinase inhibitor and assessed with biomarkers for type II collagen formation (PRO-C2) and fibronectin degradation (FBN-C).
Dynamic compression and cartilage remodeling in Bovine Cartilage Explants
Amongst others, PRO-C2 has shown that not only does mechanical loading preserve cartilage, but it also positively modulates the effect of known growth factors, such as IGF-1.
Screening potential drug candidates in physiological loading conditions could provide a more accurate translation to push forward the urgent medical need for better treatments of osteoarthritis.
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