Collagen synthesis of articular cartilage explants in response to frequency of cyclic mechanical loading

2006 ◽  
Vol 327 (1) ◽  
pp. 155-166 ◽  
Author(s):  
Amela Wolf ◽  
Beate Ackermann ◽  
Jürgen Steinmeyer
2004 ◽  
Vol 08 (01) ◽  
pp. 1-12 ◽  
Author(s):  
Andrea L. Clark ◽  
Linda Mills ◽  
David A Hart ◽  
Walter Herzog

Mechanical loading of articular cartilage affects the synthesis and degradation of matrix macromolecules. Much of the work in this area has involved mechanical loading of articular cartilage explants or cells in vitro and assessing biological responses at the mRNA and protein levels. In this study, we developed a new experimental technique to load an intact patellofemoral joint in vivo using muscle stimulation. The articular cartilages were cyclically loaded for one hour in a repeatable and measurable manner. Cartilage was harvested from central and peripheral regions of the femoral groove and patella, either immediately after loading or after a three hour recovery period. Total RNA was isolated from the articular cartilage and biological responses were assessed on the mRNA level using the reverse transcriptase-polymerase chain reaction. Articular cartilage from intact patellofemoral joints demonstrated heterogeneity at the mRNA level for six of the genes assessed independent of the loading protocol. Cyclical loading of cartilage in its native environment led to alterations in mRNA levels for a subset of molecules when assessed immediately after the loading period. However, the increases in TIMP-1 and decreases in bFGF mRNA levels were transient; being present immediately after load application but not after a three hour recovery period.


Author(s):  
Kristy T. S. Palomares ◽  
Thomas A. Einhorn ◽  
Louis C. Gerstenfeld ◽  
Elise F. Morgan

The mechanical properties of hyaline cartilage depend heavily on tissue structure and biochemical composition. Glycosaminoglycans (GAGs) and collagen fibrils are the key extracellular matrix components of hyaline cartilage that bestow compressive and tensile stiffness, respectively.[1–2] In articular cartilage, a decline in GAG content and collagen organization with injury or with diseases such as osteoarthritis is intimately linked with a decline in mechanical function.[3] In tissue-engineered cartilage and articular cartilage explants, mechanical loading in vitro results in increased aggrecan mRNA expression, GAG content, and increased stiffness.[4–6] These findings suggest that mechanical loading could be applied in vivo to promote cartilage repair via modulation of gene expression, tissue structure, and tissue composition. We have previously developed an in vivo model of skeletal repair in which application of a controlled bending motion to a healing osteotomy gap results in formation of cartilage within the gap.[6] Using this model, we sought to characterize the biochemical composition and collagen structure of the mechanically induced cartilaginous tissue. The objectives of this study were: 1) to quantify the total GAG content and aggrecan mRNA expression; and 2) to characterize the collagen fiber orientation.


Author(s):  
Agnese Ravetto ◽  
Linda M. Kock ◽  
Corrinus C. van Donkelaar ◽  
Keita Ito

High prevalence of osteoarthritis and poor intrinsic healing capacity of articular cartilage create a demand for cell-based strategies for cartilage repair. It is possible to tissue engineer cartilage with almost native proteoglycan content, but collagen reaches only 15% to 35% of the native content. Also its natural arcade-like structural organization is not reproduced. These drawbacks contribute to its insufficient load-bearing properties. It is generally believed that the application of mechanical loading during culturing will improve the mechanical properties. However, a suitable mechanical loading regime has not yet been established.


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.


1992 ◽  
Vol 288 (3) ◽  
pp. 721-726 ◽  
Author(s):  
A J Curtis ◽  
R J Devenish ◽  
C J Handley

The addition of serum or insulin-like growth factor-I (IGF-I) to the medium of explant cultures of bovine articular cartilage is known to stimulate the synthesis of aggrecan in a dose-dependent manner. The half-life of the pool of proteoglycan core protein was measured in adult articular cartilage cultured for 6 days in the presence and absence of 20 ng of IGF-I/ml and shown to be 24 min under both sets of conditions. The half-life of the mRNA pool coding for aggrecan was also determined and shown to be approx. 4 h in cartilage maintained in culture with or without IGF-I. The pool size of mRNA coding for aggrecan core protein increased 5-6-fold in cartilage explants maintained in culture in medium containing 20% (v/v) fetal-calf serum; however, in tissue maintained with medium containing IGF-I there was no increase in the cellular levels of this mRNA. This suggests that aggrecan synthesis is stimulated by IGF-I at the level of translation of mRNA coding for the core protein of this proteoglycan and that other growth factors are present in serum that stimulate aggrecan synthesis at the level of transcription of the core-protein gene. Inclusion of serum or IGF-I in the medium of cartilage explant cultures induced increases in the amounts of mRNA coding for type II collagen and link protein, whereas only serum enhanced the amount of mRNA for the core protein of decorin.


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