scholarly journals Mice Lacking the Matrilin Family of Extracellular Matrix Proteins Develop Mild Skeletal Abnormalities and Are Susceptible to Age-Associated Osteoarthritis

2020 ◽  
Vol 21 (2) ◽  
pp. 666 ◽  
Author(s):  
Ping Li ◽  
Lutz Fleischhauer ◽  
Claudia Nicolae ◽  
Carina Prein ◽  
Zsuzsanna Farkas ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Articular Cartilage ◽  
Growth Plate ◽  
Lumbar Vertebra ◽  
Adaptor Proteins ◽  
Biomechanical Properties ◽  
Dominant Negative ◽  
Endochondral Bone Formation ◽  
Appendicular Skeleton ◽  
Skeletal Phenotype

Matrilins (MATN1, MATN2, MATN3 and MATN4) are adaptor proteins of the cartilage extracellular matrix (ECM), which bridge the collagen II and proteoglycan networks. In humans, dominant-negative mutations in MATN3 lead to various forms of mild chondrodysplasias. However, single or double matrilin knockout mice generated previously in our laboratory do not show an overt skeletal phenotype, suggesting compensation among the matrilin family members. The aim of our study was to establish a mouse line, which lacks all four matrilins and analyze the consequence of matrilin deficiency on endochondral bone formation and cartilage function. Matn1-4−/− mice were viable and fertile, and showed a lumbosacral transition phenotype characterized by the sacralization of the sixth lumbar vertebra. The development of the appendicular skeleton, the structure of the growth plate, chondrocyte differentiation, proliferation, and survival were normal in mutant mice. Biochemical analysis of knee cartilage demonstrated moderate alterations in the extractability of the binding partners of matrilins in Matn1-4−/− mice. Atomic force microscopy (AFM) revealed comparable compressive stiffness but higher collagen fiber diameters in the growth plate cartilage of quadruple mutant compared to wild-type mice. Importantly, Matn1-4−/− mice developed more severe spontaneous osteoarthritis at the age of 18 months, which was accompanied by changes in the biomechanical properties of the articular cartilage. Interestingly, Matn4−/− mice also developed age-associated osteoarthritis suggesting a crucial role of MATN4 in maintaining the stability of the articular cartilage. Collectively, our data provide evidence that matrilins are important to protect articular cartilage from deterioration and are involved in the specification of the vertebral column.

Ameliorating Glycosaminoglycan (GAG) Loss and Cell Death in Articular Cartilage Following Single-Impact Loading

2007 ◽  
Author(s):  
Roman M. Natoli ◽  
Kyriacos A. Athanasiou
Keyword(s):  
Extracellular Matrix ◽  
Cell Death ◽  
Articular Cartilage ◽  
Impact Loading ◽  
Biomechanical Properties ◽  
Cartilage Explants ◽  
Single Impact ◽  
Igf I ◽  
Post Traumatic ◽  
Bioactive Agents

Impact loading of articular cartilage leads to post-traumatic osteoarthritis (OA) through its effects on the cells and extracellular matrix (ECM) of the tissue. Studies have shown the level of impact or injurious compression correlates with increased cell death, degradation of the ECM, and detrimental changes in biomechanical properties [1]. Recently, several bioactive agents, such as P188 and IGF-I, have shown promising results by reducing cell death following injurious compression of cartilage explants [2, 3].

scholarly journals Chondrocyte-specific RUNX2 Overexpression Causes Chondrodysplasia During Development, but is Not Sufficient to Induce OA-like Articular Cartilage Degeneration in Adult Mice Without Injury

2018 ◽  
Author(s):  
Sarah E. Catheline ◽  
Donna Hoak ◽  
Martin Chang ◽  
John P. Ketz ◽  
Matthew J. Hilton ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Growth Plate ◽  
Chondrocyte Apoptosis ◽  
Tunel Staining ◽  
Endochondral Bone Formation ◽  
Growth Plate Chondrocytes ◽  
Osteoarthritic Cartilage ◽  
Joint Injury ◽  
Chondrocyte Maturation ◽  
Adult Mice

ABSTRACTRUNX2 is a transcription factor critical for chondrocyte maturation and normal endochondral bone formation. It promotes the expression of factors catabolic to the cartilage extracellular matrix and is shown to be upregulated in human osteoarthritic cartilage and in murine articular cartilage following joint injury. To date, in vivo studies of RUNX2 overexpression in cartilage have been limited to forced expression in osteochondroprogenitor cells preventing investigation into the effects of chondrocyte-specific RUNX2 overexpression during development or in postnatal articular cartilage. Here, we used the Rosa26Runx2 allele in combination with the inducible Col2a1CreERT2 transgene or the inducible AcanCreERT2 knock-in allele to achieve chondrocyte-specific RUNX2 overexpression (OE) during embryonic development or in the postnatal articular cartilage of adult mice, respectively. RUNX2 OE was induced at E13.5 for all developmental studies and resulted in a phenotype resembling chondrodysplasia at E18.5. Histology and in situ hybridization analyses suggest an early onset of chondrocyte hypertrophy and accelerated terminal maturation in the limbs of the RUNX2 OE embryos compared to control embryos. Additionally, RUNX2 OE resulted in enhanced TUNEL staining indicative of increased chondrocyte apoptosis throughout all regions of the growth plate. For all postnatal studies, RUNX2 OE was induced at 2 months of age. Surprisingly, no histopathological signs of OA or cartilage catabolism were observed even six months following induction of RUNX2 OE in postnatal animals. Using the meniscal/ligamentous injury (MLI), a surgical model of knee joint destabilization and meniscal injury, however, we found that chondrocyte-specific RUNX2 OE accelerates the progression of OA pathogenesis following joint trauma. Histomorphometry and OARSI scoring confirmed decreased cartilage area two months following injury in the RUNX2 OE joints compared to control joints. Further, the numbers of MMP13-positive and TUNEL-positive chondrocytes were significantly greater in the articular cartilage of the RUNX2 OE joints compared to control joints one month following injury. Collectively, our data support that RUNX2 OE in growth plate chondrocytes is sufficient to promote their hypertrophy and terminal maturation during development. While RUNX2 overexpression alone is surprisingly insufficient to induce catabolic changes to the postnatal articular cartilage, it can accelerate the progression of post-traumatic OA. These results suggest that although increased RUNX2 expression may predetermine the rate of OA onset and/or progression following traumatic joint injury, alone this change is not sufficient to initiate the OA degenerative process.

Stress Relaxation of Cartilage Under Simple Shear and Compression: Experiments and Finite Element Analyses

2012 ◽  
Author(s):  
Chen-Yuan Chung ◽  
Mostafa Motavalli ◽  
Joseph M. Mansour
Keyword(s):  
Extracellular Matrix ◽  
Finite Element ◽  
Articular Cartilage ◽  
Simple Shear ◽  
Type Ii Collagen ◽  
Biomechanical Properties ◽  
Type Ii ◽  
Finite Element Analyses ◽  
Stress And Deformation ◽  
Engineered Cartilage

Articular cartilage is a hydrated connective tissue consisting of a relatively small number of chondrocytes surrounded by a saturated extracellular matrix comprised mainly of type-II collagen fibrils and proteoglycans. As a deformable fluid saturated material, cartilage is most often modeled using biphasic or poroelastic theories [1,2]. The ultimate goal of this work is to evaluate biomechanical properties of native and tissue engineered cartilage under combined compression and shear. The purpose of this investigation was to determine stress and deformation fields in cartilage under compression and simple shear and relate these to measured results.

scholarly journals Superficial Zone Extracellular Matrix Extracts Enhance Boundary Lubrication of Self-Assembled Articular Cartilage

Cartilage ◽  
2015 ◽  
Vol 7 (3) ◽  
pp. 256-264 ◽  
Author(s):  
Gordon Peng ◽  
Sean M. McNary ◽  
Kyriacos A. Athanasiou ◽  
A. Hari Reddi
Keyword(s):  
Extracellular Matrix ◽  
Articular Cartilage ◽  
Friction Coefficient ◽  
Culture Medium ◽  
Guanidine Hydrochloride ◽  
Biomechanical Properties ◽  
Superficial Zone ◽  
Boundary Lubricant ◽  
Exogenous Addition ◽  
Self Assembled

Objective Previous work has shown that increasing the production of boundary lubricant, superficial zone protein (SZP), did not reduce the friction coefficient of self-assembled articular cartilage constructs and was possibly due to poor retention of the lubricant. The aim of this investigation was to reduce the friction coefficient of self-assembled articular cartilage constructs through enhancing SZP retention by the exogenous addition of extracellular matrix (ECM) extracted from the superficial zone of native articular cartilage. Design Superficial zone cartilage was shaved from juvenile bovine femoral condyles using a dermatome, minced finely with razor blades, extracted with 4 M guanidine-hydrochloride, buffer exchanged with culture medium, and added directly to the culture medium of self-assembled articular cartilage constructs at low (10 µg/mL) and high (100 µg/mL) concentrations for 4 weeks. Biochemical and biomechanical properties were determined at the conclusion of 4 weeks culture. Results ECM treatment increased compressive and tensile stiffness of self-assembled articular cartilage constructs and decreased the friction coefficient. Glycosaminoglycan content decreased and collagen content increased significantly in self-assembled constructs by the ECM treatment. Conclusions Friction coefficients of self-assembled articular cartilage constructs were reduced by adding extracted superficial zone ECM into the culture medium of self-assembled articular cartilage constructs.

scholarly journals Association of an extracellular protein (chondrocalcin) with the calcification of cartilage in endochondral bone formation.

1984 ◽  
Vol 98 (1) ◽  
pp. 54-65 ◽  
Author(s):  
A R Poole ◽  
I Pidoux ◽  
A Reiner ◽  
H Choi ◽  
L C Rosenberg
Keyword(s):  
Extracellular Matrix ◽  
Bone Formation ◽  
Growth Plate ◽  
Calcium Binding ◽  
Calcium Binding Protein ◽  
Cartilage Matrix ◽  
Hypertrophic Chondrocytes ◽  
Endochondral Bone Formation ◽  
Endochondral Bone ◽  
Nucleation Sites

We examined bovine fetal epiphyseal and growth plate cartilages by immunofluorescence microscopy and immunoelectron microscopy using monospecific antibodies to a newly discovered cartilage-matrix calcium-binding protein that we now call chondrocalcin. Chondrocalcin was evenly distributed at relatively low concentration in resting fetal epiphyseal cartilage. In growth plate cartilage, it was absent from the extracellular matrix in the zone of proliferating chondrocytes but was present in intracellular vacuoles in proliferating, maturing and upper hypertrophic chondrocytes. The protein then disappeared from the lower hypertrophic chondrocytes and appeared in the adjoining extracellular matrix, where it was selectively concentrated in the longitudinal septa in precisely the same location where amorphous mineral was deposited in large amounts as demonstrated by von Kossa staining and electron microscopy. Mineral then spread out from these "nucleation sites" to occupy much of the surrounding matrix. Matrix vesicles were identified in this calcifying matrix but they bore no observable morphological relationship to these major sites of calcification where chondrocalcin was concentrated. Since chondrocalcin is a calcium-binding protein and has a strong affinity for hydroxyapatite, these observations suggest that chondrocalcin may play a fundamental role in the creation of nucleation sites for the calcification of cartilage matrix in endochondral bone formation.

Optimization of a decellularization protocol of porcine tracheas. Long-term effects of cryopreservation. A histological study

2021 ◽  
pp. 039139882110089
Author(s):  
Lara Milian ◽  
María Sancho-Tello ◽  
Joan Roig-Soriano ◽  
Giovanna Foschini ◽  
Néstor J Martínez-Hernández ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Histological Study ◽  
Biomechanical Properties ◽  
Elastic Fibers ◽  
Appreciable Effect ◽  
Long Term Effects ◽  
Minimal Impact ◽  
Biomechanical Effect ◽  
Triton X

Objective: The aim of this study was to optimize a decellularization protocol in the trachea of Sus scrofa domestica (pig) as well as to study the effects of long-term cryopreservation on the extracellular matrix of decellularized tracheas. Methods: Porcine tracheas were decellularized using Triton X-100, SDC, and SDS alone or in combination. The effect of these detergents on the extracellular matrix characteristics of decellularized porcine tracheas was evaluated at the histological, biomechanical, and biocompatibility level. Morphometric approaches were used to estimate the effect of detergents on the collagen and elastic fibers content as well as on the removal of chondrocytes from decellularized organs. Moreover, the long-term structural, ultrastructural, and biomechanical effect of cryopreservation of decellularized tracheas were also estimated. Results: Two percent SDS was the most effective detergent tested concerning cell removal and preservation of the histological and biomechanical properties of the tracheal wall. However, long-term cryopreservation had no an appreciable effect on the structure, ultrastructure, and biomechanics of decellularized tracheal rings. Conclusion: The results presented here reinforce the use of SDS as a valuable decellularizing agent for porcine tracheas. Furthermore, a cryogenic preservation protocol is described, which has minimal impact on the histological and biomechanical properties of decellularized porcine tracheas.

scholarly journals A composite scaffold of Wharton’s jelly and chondroitin sulphate loaded with human umbilical cord mesenchymal stem cells repairs articular cartilage defects in rat knee

2021 ◽  
Vol 32 (4) ◽  
Author(s):  
Zhong Li ◽  
Yikang Bi ◽  
Qi Wu ◽  
Chao Chen ◽  
Lu Zhou ◽  
...  
Keyword(s):  
Stem Cells ◽  
Articular Cartilage ◽  
Composite Scaffold ◽  
Biomechanical Properties ◽  
Cartilage Defects ◽  
Human Umbilical Cord ◽  
Composite Scaffolds ◽  
Articular Cartilage Defects

AbstractTo evaluate the performance of a composite scaffold of Wharton’s jelly (WJ) and chondroitin sulfate (CS) and the effect of the composite scaffold loaded with human umbilical cord mesenchymal stem cells (hUCMSCs) in repairing articular cartilage defects, two experiments were carried out. The in vitro experiments involved identification of the hUCMSCs, construction of the biomimetic composite scaffolds by the physical and chemical crosslinking of WJ and CS, and testing of the biomechanical properties of both the composite scaffold and the WJ scaffold. In the in vivo experiments, composite scaffolds loaded with hUCMSCs and WJ scaffolds loaded with hUCMSCs were applied to repair articular cartilage defects in the rat knee. Moreover, their repair effects were evaluated by the unaided eye, histological observations, and the immunogenicity of scaffolds and hUCMSCs. We found that in vitro, the Young’s modulus of the composite scaffold (WJ-CS) was higher than that of the WJ scaffold. In vivo, the composite scaffold loaded with hUCMSCs repaired rat cartilage defects better than did the WJ scaffold loaded with hUCMSCs. Both the scaffold and hUCMSCs showed low immunogenicity. These results demonstrate that the in vitro construction of a human-derived WJ-CS composite scaffold enhances the biomechanical properties of WJ and that the repair of knee cartilage defects in rats is better with the composite scaffold than with the single WJ scaffold if the scaffold is loaded with hUCMSCs.

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