scholarly journals Expression and Localization of Thrombospondins, Plastin 3, and STIM1 in Different Cartilage Compartments of the Osteoarthritic Varus Knee

2021 ◽  
Vol 22 (6) ◽  
pp. 3073
Author(s):  
Daniela Mählich ◽  
Anne Glasmacher ◽  
Ilka Müller ◽  
Johannes Oppermann ◽  
David Grevenstein ◽  
...  

Osteoarthritis (OA) is a multifactorial disease which is characterized by a change in the homeostasis of the extracellular matrix (ECM). The ECM is essential for the function of the articular cartilage and plays an important role in cartilage mechanotransduction. To provide a better understanding of the interaction between the ECM and the actin cytoskeleton, we investigated the localization and expression of the Ca2+-dependent proteins cartilage oligomeric matrix protein (COMP), thrombospondin-1 (TSP-1), plastin 3 (PLS3) and stromal interaction molecule 1 (STIM1). We investigated 16 patients who suffered from varus knee OA and performed a topographical analysis of the cartilage from the medial and lateral compartment of the proximal tibial plateau. In a varus knee, OA is more pronounced in the medial compared to the lateral compartment as a result of an overloading due to the malalignment. We detected a location-dependent staining of PLS3 and STIM1 in the articular cartilage tissue. The staining intensity for both proteins correlated with the degree of cartilage degeneration. The staining intensity of TSP-1 was clearly reduced in the cartilage of the more affected medial compartment, an observation that was confirmed in cartilage extracts by immunoblotting. The total amount of COMP was unchanged; however, slight changes were detected in the localization of the protein. Our results provide novel information on alterations in OA cartilage suggesting that Ca2+-dependent mechanotransduction between the ECM and the actin cytoskeleton might play an essential role in the pathomechanism of OA.

2019 ◽  
Vol 20 (5) ◽  
pp. 1008 ◽  
Author(s):  
Paolo Alberton ◽  
Hans Dugonitsch ◽  
Bastian Hartmann ◽  
Ping Li ◽  
Zsuzsanna Farkas ◽  
...  

The gene encoding the proteoglycan aggrecan (Agc1) is abundantly expressed in cartilage during development and adulthood, and the loss or diminished deposition of the protein results in a wide range of skeletal malformations. Furthermore, aggrecan degradation is a hallmark of cartilage degeneration occurring in osteoarthritis. In the present study, we investigated the consequences of a partial loss of aggrecan in the postnatal skeleton and in the articular cartilage of adult mice. We took advantage of the previously described Agc1tm(IRES-CreERT2) mouse line, which allows for conditional and timely-regulated deletion of floxed, cartilage-expressed genes. As previously reported, the introduction of the CreERT2 cassette in the 3’UTR causes a disruption of the normal expression of Agc1 resulting in a hypomorphic deposition of the protein. In homozygous mice, we observed a dwarf phenotype, which persisted throughout adulthood supporting the evidence that reduced aggrecan amount impairs skeletal growth. Homozygous mice exhibited reduced proteoglycan staining of the articular cartilage at 6 and 12 months of age, increased stiffening of the extracellular matrix at six months, and developed severe cartilage erosion by 12 months. The osteoarthritis in the hypomorph mice was not accompanied by increased expression of catabolic enzymes and matrix degradation neoepitopes. These findings suggest that the degeneration found in homozygous mice is likely due to the compromised mechanical properties of the cartilage tissue upon aggrecan reduction.


Author(s):  
Patchava Apparao ◽  
Sudhakar S ◽  
Ganapathi Swamy Ch ◽  
Ravi Shankar Reddy

Objectives: To determine the effectiveness of knee joint stabilization exercises in minimizing articular cartilage degeneration and to examine theeffectiveness of knee joint stabilization exercises on decreasing pain, improving range of motion (ROM) and muscle strength.Methods: About 20 volunteer subjects (age 35-65 years) with primary osteoarthritis fulfilled the inclusion criteria given the knee stabilizationexercises for 8 weeks. Pain, muscle strength, functional outcome score, and serum cartilage oligomeric matrix protein (COMP) values were measuredpre- and post-intervention using visual analog scale, dynamometer, and ELISA test. Data were analyzed using a paired t-test with Statistical Packagefor the Social Sciences version 20 to find out the difference between the pre- and post-test.Results: The results of the study have shown that significant difference between pre- and post-test values of pain, ROM, muscle strength and functionaloutcome score with p<0.05, and there is statistical in significance in serum COMP value (p<0.05).Conclusion: Stabilization exercises of knee joint were shown to be beneficial for decreasing pain, improving ROM and muscle strength, and there wasno effect on articular cartilage changes in degenerative tibiofemoral joint disease.Keywords: Serum cartilage oligomeric matrix protein, Knee stabilization exercises, Proprioception exercises, Muscle strength.  


2002 ◽  
Vol 50 (10) ◽  
pp. 1313-1323 ◽  
Author(s):  
Ghada A. Nofal ◽  
Cheryl B. Knudson

The proteoglycan-rich extracellular matrix (ECM) directly associated with the cells of articular cartilage is anchored to the chondrocyte plasma membrane via interaction with the hyaluronan receptor CD44. The cytoplasmic tail of CD44 interacts with the cortical cytoskeleton. The objective of this study was to determine the role of the actin cytoskeleton in CD44-mediated matrix assembly by chondrocytes and cartilage matrix retention and homeostasis. Adult bovine articular cartilage tissue slices and isolated chondrocytes were treated with latrunculin or cytochalasin. Tissues were processed for histology and chondrocytes were examined for CD44 expression and pericellular matrix assembly. Treatments that disrupt the actin cytoskeleton reduced chondrocyte pericellular matrix assembly and the retention of proteoglycan within cartilage explants. There was enhanced detection of a neoepitope resulting from proteolysis of aggrecan. Cytoskeletal disruption did not reduce CD44 expression, as monitored by flow cytometry, but detergent extraction of CD44 was enhanced and hyaluronan binding was decreased. Thus, disruption of the cytoskeleton reduces the anchorage of CD44 in the chondrocyte membrane and the capacity of CD44 to bind its ligand. The results suggest that cytoskeletal disruption within cartilage uncouples chondrocytes from the matrix, resulting in altered metabolism and deleterious changes in matrix structure.


2020 ◽  
Author(s):  
XIAOJIAN WANG ◽  
LEI WEI ◽  
XIAOCHUN WEI ◽  
YAN XUE ◽  
ZHIQIANG ZHANG ◽  
...  

Abstract During the development of knee osteoarthritis(OA), chondrocyte colony-like clusters occur in cartilage tissue. However, the significance of chondrocyte colony-like cluster formation in cartilage tissue remains unclear. In these studies,we investigated the timing and location of chondrocyte colony-like clusters in cartilage tissue during the development of human knee OA,and explored the biological properties of chondrocytes in colony-like clusters and their significance for degenerative cartilage tissue. The resulte showed that chondrocyte colony-like clusters mainly formed in the OARSI grades 3 and 4 cartilage tissue,which could divide into four stages according to the quantity and biological properties of the chondrocytes inside the cluster.The chondrocyte colony-like clusters in cartilage tissue could cause the cartilage tissue to become looser and more porous, with more severe cartilage degeneration. To understand this, we further clarified the development of this disease and provided a new direction for the treatment of knee OA.


Author(s):  
Theodore W. Vandenberg ◽  
Christopher R. Nehme ◽  
Thomas P. James

Articular cartilage degeneration is a central pathological feature of osteoarthritis. Cartilage in the adult does not regenerate in vivo and, as a result, cartilage damage in osteoarthritis is irreversible. With our ever-aging population, osteoarthritis has become a leading cause of disability and unfortunately, no optimal treatments for osteoarthritis are currently available. To address this problem, a research community is focused on the development of both natural and synthetic biodegradable tissue scaffolds. The scaffolds must contain depressions or holes for the purpose of chondrocyte seeding and growth in order to create an implantable construct. In addition to chondrocytes, cartilage tissue consists of the extracellular matrix (ECM). Studies of many tissue types have established that ECM plays an important role in regulating cell behavior and controlling processes such as tissue differentiation and tumor progression. Unlike most natural tissues, adult cartilage ECM is exceptionally dense and lacking in vascularity, which makes it difficult for chondrocytes to be transplanted directly into the matrix. Current methods of creating cell home sites through chemical decellularization of the ECM degrade the mechanical integrity of the cartilage tissue. The research conducted here used a mechanical, rather than chemical, method to create cell home sites. A novel micropunching machine was developed to fabricate 200 μm diameter holes in cartilage, thereby creating a porous natural scaffold while maintaining a healthy ECM. Equine articular cartilage slices were harvested from the cadaver’s back knee joint and cryo-sectioned into 100 μm thick slices. Using die clearances of 3.7%, 6.8%, and 8.9%, the results indicate that micro-scale holes can be mechanically punched in cartilage tissue. The maximum punching force showed a slight trend of decreasing as die clearance increased, but there was no statistical significance. Punching force, as well as hole size, was highly dependent on sample hydration. Upon inspection, the resulting hole sizes were approximately 50 μm to 150 um, indicating 25% to 75% shrinkage in reference to the male punch diameter. Finally, the resulting hole shape was observed to be slightly non-circular and the edges of the hole exhibited a raggedness, which was indicative of the cartilage tearing during hole punching.


PLoS ONE ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. e0246395
Author(s):  
Doaa Youssef ◽  
Salah Hassab-Elnaby ◽  
Hatem El-Ghandoor

Quantitative measurement of nanoscale surface roughness of articular cartilage tissue is significant to assess the surface topography for early treatment of osteoarthritis, the most common joint disease worldwide. Since it was not established by clinical diagnostic tools, the current studies have been suggesting the use of alternative diagnostic tools using pre-clinical methods. This study aims to measure the nanoscale surface roughness of articular cartilage tissue utilizing biospeckle which is used as a non-destructive and non-contact optical imaging technique. An experimental setup was implemented to capture biospeckle images from twelve cross-section areas of articular cartilage tissue gathered from bovine knee joints at 632 nm wavelength laser radiation. Then, to analyze the biospeckle image, a second-order statistical-based method was proposed through the combination of 308 highly correlated statistical features extracted from implemented gray-level co-occurrence matrices by employing principal component analysis. The result indicated that the measurement of the nanoscale surface roughness based on the first principal component only is able to provide accurate and precise quantitative measurement of early signs of articular cartilage degeneration up to 2500 nm.


2020 ◽  
Author(s):  
Vesa Virtanen ◽  
Ervin Nippolainen ◽  
Rubina Shaikh ◽  
Isaac Afara ◽  
Juha Töyräs ◽  
...  

AbstractArticular cartilage (AC) is a soft connective tissue that covers the ends of articulating bones. Joint injuries may lead to degeneration of cartilage tissue and initiate development of post-traumatic osteoarthritis (OA). Arthroscopic surgeries can be used to treat joint injuries, but arthroscopic evaluation of cartilage quality is subjective. Therefore, new methods are needed for objective assessment of cartilage degeneration. Fourier transform infrared (FTIR) spectroscopy can be used to assess tissue composition based on the fundamental molecular vibrations. When combined with fiber optics and attenuated total reflectance (ATR) crystal, the measurements can be done flexibly without any sample processing. We hypothesize that Fourier transform infrared attenuated total reflection (FTIR-ATR) spectroscopy can detect enzymatically and mechanically induced changes similar to changes occurring during progression of OA. Fresh bovine patellar cartilage plugs (n = 60) were extracted and degraded enzymatically and mechanically. Adjacent untreated control samples (n = 60) were utilized as controls. Enzymatic degradation was implemented by 90-min and 24-hour collagenase as well as 30-min trypsin treatments. Mechanical damage was induced by: 1) dropping a weight impactor on the cartilage plugs, and 2) abrading the cartilage surface with a rotating sandpaper. Fiber optic FTIR-ATR spectroscopic measurements were conducted for control and degraded samples, and spectral changes were assessed with random forest (RF), partial least squares discriminant analysis (PLS-DA), and support vector machine (SVM) classifiers. RF (accuracy 93.1 % to 79.2 %), PLS-DA (accuracy 95.8% to 81.9%), and SVM (accuracy 91.7% to 80.6%) all had excellent classification performance for detecting the different enzymatic and mechanical damage on cartilage matrix. The results suggest that fiber optic FTIR-ATR spectroscopy is a viable way to detect minor degeneration of AC.


1999 ◽  
Vol 12 (02) ◽  
pp. 56-63 ◽  
Author(s):  
C. R. Bellenger ◽  
P. Ghosh ◽  
Y. Numata ◽  
C. Little ◽  
D. S. Simpson

SummaryTotal medial meniscectomy and caudal pole hemimeniscectomy were performed on the stifle joints of twelve sheep. The two forms of meniscectomy produced a comparable degree of postoperative lameness that resolved within two weeks of the operations. After six months the sheep were euthanatised and the stifle joints examined. Fibrous tissue that replaced the excised meniscus in the total meniscectomy group did not cover as much of the medial tibial condyle as the residual cranial pole and caudal fibrous tissue observed following hemimeniscectomy. The articular cartilage from different regions within the joints was examined for gross and histological evidence of degeneration. Analyses of the articular cartilage for water content, glycosaminoglycan composition and DNA content were performed. The proteoglycan synthesis and release from explanted articular cartilage samples in tissue culture were also measured. There were significant pathological changes in the medial compartment of all meniscectomised joints. The degree of articular cartilage degeneration that was observed following total meniscectomy and caudal pole meniscectomy was similar. Caudal pole hemimeniscectomy, involving transection of the meniscus, causes the same degree of degeneration of the stifle joint that occurs following total meniscectomy.The effect of total medial meniscectomy versus caudal pole hemimeniscectomy on the stifle joint of sheep was studied experimentally. Six months after the operations gross pathology, histopathology, cartilage biochemical analysis and the rate of proteoglycan synthesis in tissue culture were used to compare the articular cartilage harvested from the meniscectomised joints. Degeneration of the articular cartilage from the medial compartment of the joints was present in both of the groups. Caudal pole hemimeniscectomy induces a comparable degree of articular cartilage degeneration to total medial meniscectomy in the sheep stifle joint.


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