Abstract
(1) Background: 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 aim of this study was to investigate the effects of intermittent dynamic compression on the extracellular matrix during long-term culture of bovine cartilage explants. (2) Methods: Bovine articular cartilage explants were cultured for 21 days and subjected to 20 min of 1 Hz cyclic compressive loading five consecutive days each week. 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). (3) Results: Compression of cartilage explants increased the release of PRO-C2 and FBN-C to the conditioned media and, furthermore, IGF-1 and compression synergistically increased PRO-C2 release. Inhibition of ALK5 blocked PRO-C2 and FBN-C release in dynamically compressed explants. (4) Conclusions: Dynamic compression of cartilage explants increases both type II collagen formation and fibronectin degradation, and IGF-1 interacts synergistically with compression, increasing the overall impact on cartilage formation. These data show that mechanical loading is important to consider in translational cartilage models.
Highlights
Osteoarthritis (OA) is characterized by progressive deterioration of synovial joint tissues, including articular cartilage, synovium, ligaments and subchondral bone [1]
We examined the effects on the cartilage matrix by biomarker measurements of type II collagen formation (PRO-C2) and fibronectin turnover (FBN-C) in the conditioned media from explants
We further investigated how long-term intermittent dynamic compression modulated the matrix in response to Insulin-like growth factor-1 (IGF-1) and TGF-β1
Summary
Osteoarthritis (OA) is characterized by progressive deterioration of synovial joint tissues, including articular cartilage, synovium, ligaments and subchondral bone [1]. Synovial joints are load-bearing organs, and the principal function of articular cartilage is to transfer load with a low coefficient of friction [2]. The importance of mechanical loading for cartilage health is reflected in the large body of literature describing how various forms of joint loading exercises alleviate pain and improve function in OA patients [3,4,5]. Conditions that lead to excessive cartilage loading, such as joint instability or meniscus resection, are, detrimental and lead to degenerative changes in cartilage morphology that greatly increase the risk of
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