scholarly journals EGFR signaling is critical for maintaining the superficial layer of articular cartilage and preventing osteoarthritis initiation

2017 ◽  
Vol 25 ◽  
pp. S61-S62
Author(s):  
H. Jia ◽  
X. Ma ◽  
W. Tong ◽  
B. Doyran ◽  
Z. Sun ◽  
...  
2016 ◽  
Vol 113 (50) ◽  
pp. 14360-14365 ◽  
Author(s):  
Haoruo Jia ◽  
Xiaoyuan Ma ◽  
Wei Tong ◽  
Basak Doyran ◽  
Zeyang Sun ◽  
...  

Osteoarthritis (OA) is the most common joint disease, characterized by progressive destruction of the articular cartilage. The surface of joint cartilage is the first defensive and affected site of OA, but our knowledge of genesis and homeostasis of this superficial zone is scarce. EGFR signaling is important for tissue homeostasis. Immunostaining revealed that its activity is mostly dominant in the superficial layer of healthy cartilage but greatly diminished when OA initiates. To evaluate the role of EGFR signaling in the articular cartilage, we studied a cartilage-specific Egfr-deficient (CKO) mouse model (Col2-Cre EgfrWa5/flox). These mice developed early cartilage degeneration at 6 mo of age. By 2 mo of age, although their gross cartilage morphology appears normal, CKO mice had a drastically reduced number of superficial chondrocytes and decreased lubricant secretion at the surface. Using superficial chondrocyte and cartilage explant cultures, we demonstrated that EGFR signaling is critical for maintaining the number and properties of superficial chondrocytes, promoting chondrogenic proteoglycan 4 (Prg4) expression, and stimulating the lubrication function of the cartilage surface. In addition, EGFR deficiency greatly disorganized collagen fibrils in articular cartilage and strikingly reduced cartilage surface modulus. After surgical induction of OA at 3 mo of age, CKO mice quickly developed the most severe OA phenotype, including a complete loss of cartilage, extremely high surface modulus, subchondral bone plate thickening, and elevated joint pain. Taken together, our studies establish EGFR signaling as an important regulator of the superficial layer during articular cartilage development and OA initiation.


Author(s):  
Tomoya Susa ◽  
Ryosuke Nansai ◽  
Norimasa Nakamura ◽  
Hiromichi Fujie

Since the healing capacity of articular cartilage is limited, it is important to develop cell-based therapies for the repair of cartilage. Although synthetic or animal-derived scaffolds are frequently used for effective cell delivery long-term safety and efficiency of such scaffolds still remain unclear. We have been studying on a scaffold-free tissue engineered construct (TEC) bio-synthesized from synovium-derived mesenchymal stem cells (MSCs) [1]. As the TEC specimen is composed of cells with their native extracellular matrix, we believe that it is free from concern regarding long term immunological effects. our previous studies indicated that a porcine partial thickness chondral defect was successfully repaired with TEC but that the compressive property of the TEC-treated cartilage-like repaired tissue was different from normal cartilage in both immature and mature animals. Imura et al. found that the permeability of the immature porcine cartilage-like tissues repaired with TEC recovered to normal level for 6 months except the superficial layer [2]. Therefore, the present study was performed to determine the depth-dependent permeability of mature porcine cartilage-like tissue repaired with TEC. Moreover, we investigated the effect of difference of permeability on the compressive property of articular cartilage using a finite element analysis (FEM).


2021 ◽  
Vol 2130 (1) ◽  
pp. 012009
Author(s):  
R Karpiński ◽  
P Krakowski ◽  
J Jonak ◽  
A Machrowska ◽  
M Maciejewski ◽  
...  

Abstract Osteoarthritis (OA) is currently the most generic form of joint disease. It is a complex process in which degenerative changes occur in the articular cartilage [AC], subchondral bone, and synovial membrane and can lead to permanent joint failure. The primary and most commonly used method of diagnosing degenerative changes is classic radiography. Magnetic resonance imaging (MRI) may be used to assess the extent of damage to joint surfaces, but this method is limited by the availability of specialised equipment and the excessive cost of the examination. Arthroscopy, an invasive procedure, is considered the “gold standard” in joint diagnosis. The occurrence of degenerative changes is closely related to the friction and lubrication processes within the joint. The main causes of osteoarthritis are a change or lack of synovial fluid, deformation of the joint bones, local damage to the articular cartilage, and a change in the mechanical properties of the articular cartilage due to water loss from the damaged superficial layer. An alternative, non-invasive method that allows for a delicate assessment of the condition of moving joints is vibroarthrography (VAG). The analysis of vibroacoustic signals generated by moving joint surfaces has an immense potential in the non-invasive assessment of the degree of damage to articular cartilage, meniscus and ligaments and the general diagnosis of degenerative diseases. The purpose of this study is to analyse and statistically compare the basic characteristics of vibroacoustic signals recorded with a CM-01B contact microphone placed on the patella for motion in the 90°–0°–90° range in a closed kinetic chain (CKC) in a control group (HC) and a group of patients diagnosed with osteoarthritis (OA), qualified for the knee alloplasty.


1997 ◽  
Vol 34 (4) ◽  
pp. 271-278 ◽  
Author(s):  
N. H. M. T. Peperkamp ◽  
W. J. M. Landman ◽  
P. C. J. Tooten ◽  
A. Ultee ◽  
W. F. Voorhout ◽  
...  

Amyloid arthropathy has been recently recognized as a spontaneous syndrome in chickens. Predominantly, femorotibial and tarsometatarsal joints were affected, showing (peri) articular orange amyloid deposits. Immunohistochemical evaluation revealed the amyloid to be of the reactive type. Induction of amyloid arthropathy in chickens was carried out using a single intravenous injection of Enterococcus faecalis cultures. In the naturally occurring and the induced cases, amyloid deposits were found in the hypertrophic synovial villi and in the articular cartilage, particularly in the superficial layer and in the nutritional blood vessel walls. Highly sulfated glycosaminoglycans (GAGs) were found in the amyloid deposits. Ultrastructurally, bundles of amyloid fibrils were seen in invaginations of synoviocytes and chondrocytes. Immunogold electron microscopy failed to reveal signs of intracellular amyloid formation. The predilection site for amyloid deposition in the major leg joints of the chickens with reactive amyloid could be explained by the arthritic condition caused by Enterococcus faecalis bacteriaemia. The polyarthritis triggers hepatic acute phase protein synthesis and increases the vascular serum amyloid A (SAA) supply to the joint. Inflammatory and degenerative changes in the articular cartilage and adjoining tissues result in an increase of highly sulphated GAGs, which are considered to enhance deposition of SAA as amyloid.


1974 ◽  
Vol 52 (7) ◽  
pp. 803-804 ◽  
Author(s):  
H. U. Cameron

The intervertebral joint of the longnose gar has been examined by differential histological staining techniques and by scanning electron microscopy. The joint was found to be transitional, being neither a true diarthrosis nor a synchondrosis. The articular cartilage was found to consist of two layers, a superficial layer of fibrocartilage and a deeper layer of hyaline cartilage. The joint cavity was partially filled with fibrocartilaginous adhesions, the number of which varied from joint to joint.The degree of movement in each joint was minimal, in keeping with the heavily armored exoskeleton.


1995 ◽  
Vol 77-B (3) ◽  
pp. 460-464 ◽  
Author(s):  
R Teshima ◽  
T Otsuka ◽  
N Takasu ◽  
N Yamagata ◽  
K Yamamoto

2013 ◽  
Vol 395-396 ◽  
pp. 654-657
Author(s):  
Peng Peng Xiao ◽  
Li Lan Gao ◽  
Zhi Dong Liu ◽  
Chun Qiu Zhang

As a viscoelastic and nonlinear connective tissue, articular cartilage bears continuous sliding load in the daily activities. The optimized digital image correlation (DIC) technique was applied to investigate the effect of sliding rate and compressive strain on the normal displacement of different layers in pig articular cartilage under sliding load. The normal displacements of different layers in cartilage increase gradually with sliding going on with given sliding rate and compressive strain. Experiments showed that the normal displacement of superficial layer is the largest, the normal displacement of deep layer is the smallest and the normal displacement of middle layer is between superficial layer and deep layer, and found that the normal displacements of different layers in cartilage increase with increasing compressive strains, but decrease with increasing sliding rates. The normal displacement of different layers are different under continuous sliding load.


2019 ◽  
Author(s):  
Melina Rodrigues Bellini ◽  
Michael Andrew Pest ◽  
Jae-Wook Jeong ◽  
Frank Beier

ABSTRACTBackgroundMitogen-inducible gene 6 (Mig-6) is a tumour suppressor gene that is also associated with the development of osteoarthritis (OA)-like disorder. Recent evidence from our lab and others showed that cartilage-specific Mig-6 knockout (KO) mice develop chondro-osseous nodules, along with increased articular cartilage thickness and enhanced EGFR signaling in the articular cartilage. Here, we evaluate the phenotype of mice with skeletal-specific overexpression of Mig-6.MethodsSynovial joint tissues of the knee were assessed in 12 and 36 weeks-old skeleton-specific Mig-6 overexpressing (Mig-6over/over) and control animals using histological stains, immunohistochemistry, semi-quantitative OARSI scoring, and microCT for skeletal morphometry. Measurement of articular cartilage and subchondral bone thickness were also performed using histomorphometry.ResultsOur results show only subtle developmental effects of Mig-6 overexpression. However, male Mig-6over/over mice show accelerated cartilage degeneration at 36 weeks of age, in both medial and lateral compartments of the knee. Immunohistochemistry for SOX9 and PRG4 showed decreased staining in Mig-6over/over mice relative to controls, providing potential molecular mechanisms for the observed effects.ConclusionOverexpression of Mig-6 in articular cartilage causes no major developmental phenotype but results in accelerated development of OA during aging. These data demonstrate that precise regulation of the Mig-6/EGFR pathway is critical for joint homeostasis.


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