Session Title: Osteoarthritis and Joint Biology – Basic Science Poster II
Session Type: ACR Poster Session C
Session Time: 9:00AM-11:00AM
Background/Purpose: Mechanical loading is recognized as a major factor in initiation and progression of osteoarthritis (OA). Conversely loading is believed to play an essential role in maintaining homeostasis of healthy cartilage. Given the biomechanical function of articular cartilage and the mechanosensitivity of chondrocytes, physiological loading may be of importance in a translational cartilage model and hereby, in development of new OA drug candidates. This study investigated the effect of long-term dynamic ex vivo compression on articular cartilage through quantification of type II collagen formation and degradation.
Methods: Full-depth bovine cartilage explants were cultured for 5 weeks. The explants were treated 3 times a week with either OSM [10 ng/mL] and TNF-a [2 ng/mL] (O+T), or TGF-β1 [50 ng/mL]. Untreated samples were included as negative controls (w/o). For each condition, two groups were established; an unloaded group and a group compressed 3 times a week. Compression was applied using Electroforce 5500® (TA Instruments), in a sine wave with a maximum load per cycle of 1 MPa, at 1 Hz frequency for 1200 cycles. Metabolic activity was measured once a week using AlamarBlue. Biomarkers released to the supernatant were assessed using ELISAs: Pro-C2 and C2M for measurement of type II collagen formation and degradation respectively.
Results: Compression resulted in increased Pro-C2 release throughout the 5 weeks, peaking at week 3 where application of compression without treatment increased the Pro-C2 level 125 % (p=0.0025) above the unloaded group. A synergistic effect was observed with compression and TGF-β treatment, increasing the Pro-C2 release by 60% at week 5 (p=0.0048) compared to the non-compressed TGF-β treated samples. O+T treatment stimulated a catabolic response in the cartilage explants as shown by the increase in C2M levels. This O+T-induced C2M release was partly blocked by dynamic compression. At week 4, the C2M response was reduced by 61 % (p=0.0054) in compressed O+T treated explants compared to the non-compressed O+T treated group.
Conclusion: Long-term dynamic compression induced an increase in type II collagen formation, which was synergistic with the effect of TGF-beta. Furthermore, compression induced a reduction in cytokine-induced type II collagen degradation. In conclusion, compression stimulates formation and attenuates degradation, which may be important when evaluating the mechanisms of different novel drug candidate targeted cartilage metabolism.
To cite this abstract in AMA style:Engstrøm A, Bay-Jensen AC, Karsdal MA, Thudium CS. Dynamic Compression of Articular Cartilage Explants Increases Formation and Decreases Degradation of Type II Collagen [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 10). https://acrabstracts.org/abstract/dynamic-compression-of-articular-cartilage-explants-increases-formation-and-decreases-degradation-of-type-ii-collagen/. Accessed June 6, 2020.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/dynamic-compression-of-articular-cartilage-explants-increases-formation-and-decreases-degradation-of-type-ii-collagen/