scholarly journals Intermittent Dynamic Compression Confers Anabolic Effects in Articular Cartilage

2021 ◽  
Vol 11 (16) ◽  
pp. 7469
Author(s):  
Amalie Engstrøm ◽  
Frederik S. Gillesberg ◽  
Solveig S. Groen ◽  
Peder Frederiksen ◽  
Anne-Christine Bay-Jensen ◽  
...  

(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.

2019 ◽  
Author(s):  
XIANG JI ◽  
Akira Ito ◽  
Akihiro Nakahata ◽  
Kohei Nishitani ◽  
Hiroshi Kuroki ◽  
...  

Abstract Background This study aimed to examine the effects of a single episode of in vivo cyclic loading on rat knee articular cartilage (AC) in mid-term observation and investigate relevant factors associated with the progression of post-traumatic osteoarthritis (PTOA). Methods Twelve-week-old Wistar rats underwent one episode of 60 cycles of dynamic compression of 20 N or 50 N on their right knee joint. The spatiotemporal changes in the AC after loading were evaluated using histology and immunohistochemistry at 3 days, 1, 2, 4 and 8 weeks after loading (n=6 for each condition). The chondrocyte vitality was assessed at 1, 3, 6 and 12 hours after loading (n=2 for each condition). ResultsA localized AC lesion on lateral femoral condyle was confirmed in all subjects. The surface and intermediate cartilage in the affected area degenerated after loading, yet the calcified cartilage remained intact. The expression of type II collagen in the lesion cartilage was upregulated after loading, whereas the superficial lubricin layer was eroded in response to cyclic compression. However, the distribution of superficial lubricin gradually recovered to the normal level 4 weeks after loading-induced injury.ConclusionWe confirmed that 60 times cyclic loading exceeding 20 N could result in cartilage damage in rat knee. Endogenous repairs in well-structured joints work well with rebuilding protective layers on the lesion cartilage surface, which could be the latent factor in delaying the progression of PTOA.


Author(s):  
Nazli Caner ◽  
Jeffrey W. Ruberti

Articular cartilage is a specialized avascular connective tissue found at the contact regions of diarthrodial joints. Cartilage has few cells (< 5% of the volume), though these cells can maintain the balance of turnover in healthy tissue, when the tissue is damaged, they are not able to repair the defects [1–3]. Extra cellular matrix (ECM) in cartilage comprises water, collagen (principally type II), proteoglycans and noncollagenous proteins. The type II collagen network, which is the dominant structural protein in cartilage ECM, constrains the expansion of the resident PGs and is generally held in mechanical tension. In osteoarthritis (OA), the balance of cartilage tissue production/degradation is thought to be affected by abnormal mechanical stimuli leading to net matrix resorption through production of excess degradative enzymes (e.g. matrix metalloproteinases (MMP) and aggrecanases) [4–8]. In OA tissue the amount of MMP-13 is thought to be increased relative to healthy tissue. OA typically occurs in older adults where, as cartilage ages, there is a marked decrease in the fixed charge density (FCD), the hydration and, consequently, mechanical tension on the collagen type II network [9–11]. We have hypothesized that loss of tension on the collagen network accelerates degradation by MMP. Detection of the effect of MMP on loaded, native cartilage could lead to insight about cartilage degradation kinetics in OA. However, it is quite difficult to controllably deliver MMP to cartilage, to activate the MMP during detensioning of the collagen network and to detect the effect on the cartilage mechanics (because cost limits the amount of MMP used). We have developed a transpirational enzyme loading method which is capable of precisely dosing bovine cartilage explants with a small, known quantity of MMP-13. Following enzyme insertion, we are able to detect the activity of the MMP on osmotically compressed cartilage (i.e. cartilage with a detensioned collagen network) via a simple hydration measurement.


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