scholarly journals Comparative Effectiveness of Structural versus Regulatory Protein Gene Transfer on Articular Chondrocyte Matrix Gene Expression

Cartilage ◽  
2017 ◽  
Vol 10 (1) ◽  
pp. 102-110 ◽  
Author(s):  
Shuiliang Shi ◽  
Congrong Wang ◽  
Albert Chan ◽  
Kashif Kirmani ◽  
George J. Eckert ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Gene Transfer ◽  
Cartilage Repair ◽  
Articular Chondrocytes ◽  
Type Ii Collagen ◽  
Matrix Proteins ◽  
Type Ii ◽  
Articular Cartilage Repair ◽  
Regulatory Factors ◽  
Igf I

Objective The production of extracellular matrix is a necessary component of articular cartilage repair. Gene transfer is a promising method to improve matrix biosynthesis by articular chondrocytes. Gene transfer may employ transgenes encoding regulatory factors that stimulate the production of matrix proteins, or may employ transgenes that encode the proteins themselves. The objective of this study was to determine which of these 2 approaches would be the better choice for further development. We compared these 2 approaches using the transgenes encoding the structural matrix proteins, aggrecan or type II collagen, and the transgene encoding the anabolic factor, insulin-like growth factor I (IGF-I). Methods We transfected adult bovine articular chondrocytes with constructs encoding type II collagen, aggrecan, or IGF-I, and measured the expression of type II collagen ( COL2A1) and aggrecan ( ACAN) from their native genes and from their transgenes. Results IGF-I gene ( IGF1) transfer increased the expression of the native chondrocyte COL2A1 and ACAN genes 2.4 and 2.9 times control, respectively. COL2A1 gene transfer did not significantly increase COL2A1 transcripts, even when the transgene included the genomic COL2A1 regulatory sequences stimulated by chondrogenic growth factors. In contrast, ACAN gene transfer increased ACAN transcripts up to 3.4 times control levels. IGF1, but not ACAN, gene transfer increased aggrecan protein production. Conclusion Taken together, these results suggest that the type II collagen and aggrecan production required for articular cartilage repair will be more effectively achieved by genes that encode anabolic regulatory factors than by genes that encode the matrix molecules themselves.

Facilitating In Vivo Articular Cartilage Repair by Tissue-Engineered Cartilage Grafts Produced From Auricular Chondrocytes

2017 ◽  
Vol 46 (3) ◽  
pp. 713-727 ◽  
Author(s):  
Chin-Chean Wong ◽  
Chih-Hwa Chen ◽  
Li-Hsuan Chiu ◽  
Yang-Hwei Tsuang ◽  
Meng-Yi Bai ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Articular Cartilage ◽  
Cartilage Repair ◽  
Articular Chondrocytes ◽  
Type Ii Collagen ◽  
Type Ii ◽  
Articular Cartilage Repair ◽  
3 Dimensional ◽  
Cell Conversion

Background: Insufficient cell numbers still present a challenge for articular cartilage repair. Converting heterotopic auricular chondrocytes by extracellular matrix may be the solution. Hypothesis: Specific extracellular matrix may convert the phenotype of auricular chondrocytes toward articular cartilage for repair. Study Design: Controlled laboratory study. Methods: For in vitro study, rabbit auricular chondrocytes were cultured in monolayer for several passages until reaching status of dedifferentiation. Later, they were transferred to chondrogenic type II collagen (Col II)–coated plates for further cell conversion. Articular chondrogenic profiles, such as glycosaminoglycan deposition, articular chondrogenic gene, and protein expression, were evaluated after 14-day cultivation. Furthermore, 3-dimensional constructs were fabricated using Col II hydrogel-associated auricular chondrocytes, and their histological and biomechanical properties were analyzed. For in vivo study, focal osteochondral defects were created in the rabbit knee joints, and auricular Col II constructs were implanted for repair. Results: The auricular chondrocytes converted by a 2-step protocol expressed specific profiles of chondrogenic molecules associated with articular chondrocytes. The histological and biomechanical features of converted auricular chondrocytes became similar to those of articular chondrocytes when cultivated with Col II 3-dimensional scaffolds. In an in vivo animal model of osteochondral defects, the treated group (auricular Col II) showed better cartilage repair than did the control groups (sham, auricular cells, and Col II). Histological analyses revealed that cartilage repair was achieved in the treated groups with abundant type II collagen and glycosaminoglycans syntheses rather than elastin expression. Conclusion: The study confirmed the feasibility of applying heterotopic chondrocytes for cartilage repair via extracellular matrix–induced cell conversion. Clinical Relevance: This study proposes a feasible methodology to convert heterotopic auricular chondrocytes for articular cartilage repair, which may serve as potential alternative sources for cartilage repair.

scholarly journals Natural Type II Collagen Hydrogel, Fibrin Sealant, and Adipose-Derived Stem Cells as a Promising Combination for Articular Cartilage Repair

Cartilage ◽  
2016 ◽  
Vol 8 (4) ◽  
pp. 439-443 ◽  
Author(s):  
Mariana Lazarini ◽  
Pedro Bordeaux-Rego ◽  
Renata Giardini-Rosa ◽  
Adriana S. S. Duarte ◽  
Mariana Ozello Baratti ◽  
...  
Keyword(s):  
Stem Cells ◽  
Articular Cartilage ◽  
Cartilage Repair ◽  
Fibrin Sealant ◽  
Type Ii Collagen ◽  
Adipose Derived Stem Cells ◽  
Type Ii ◽  
Articular Cartilage Repair ◽  
Collagen Hydrogel

Objective Articular cartilage is an avascular tissue with limited ability of self-regeneration and the current clinical treatments have restricted capacity to restore damages induced by trauma or diseases. Therefore, new techniques are being tested for cartilage repair, using scaffolds and/or stem cells. Although type II collagen hydrogel, fibrin sealant, and adipose-derived stem cells (ASCs) represent suitable alternatives for cartilage formation, their combination has not yet been investigated in vivo for focal articular cartilage defects. We performed a simple experimental procedure using the combination of these 3 compounds on cartilage lesions of rabbit knees. Design The hydrogel was developed in house and was first tested in vitro for chondrogenic differentiation. Next, implants were performed in chondral defects with or without ASCs and the degree of regeneration was macroscopically and microscopically evaluated. Results Production of proteoglycans and the increased expression of collagen type II (COL2α1), aggrecan (ACAN), and sex-determining region Y-box 9 (SOX9) confirmed the chondrogenic character of ASCs in the hydrogel in vitro. Importantly, the addition of ASC induced a higher overall repair of the chondral lesions and a better cellular organization and collagen fiber alignment compared with the same treatment without ASCs. This regenerating tissue also presented the expression of cartilage glycosaminoglycan and type II collagen. Conclusions Our results indicate that the combination of the 3 compounds is effective for articular cartilage repair and may be of future clinical interest.

Articular cartilage repair with recombinant human type II collagen/polylactide scaffold in a preliminary porcine study

2015 ◽  
Vol 34 (5) ◽  
pp. 745-753 ◽  
Author(s):  
Virpi Muhonen ◽  
Eve Salonius ◽  
Anne-Marie Haaparanta ◽  
Elina Järvinen ◽  
Teemu Paatela ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Cartilage Repair ◽  
Type Ii Collagen ◽  
Type Ii ◽  
Articular Cartilage Repair ◽  
Human Type

scholarly journals 165 DIRECT RAAV-MEDIATED IGF-I OVEREXPRESSION ENHANCES ARTICULAR CARTILAGE REPAIR IN VIVO

2010 ◽  
Vol 18 ◽  
pp. S81
Author(s):  
M. Cucchiarini ◽  
M.D. Menger ◽  
D. Kohn ◽  
S.B. Trippel ◽  
E.F. Terwilliger ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Cartilage Repair ◽  
Articular Cartilage Repair ◽  
Igf I

scholarly journals Inhibition of activity of collagen degradation in cartilage of patients with osteoarthrosis byactivation of glycolysis

2011 ◽  
Vol 14 (1) ◽  
pp. 8-12
Author(s):  
E. V. Chetina ◽  
E. V. Chetina
Keyword(s):  
Articular Cartilage ◽  
Dna Synthesis ◽  
Articular Chondrocytes ◽  
Type Ii Collagen ◽  
Cartilage Destruction ◽  
Cartilage Explants ◽  
Type Ii ◽  
Cleavage Activity ◽  
Articular Cartilages ◽  
Elisa Inhibition

Aim. To study the effect of glycolysis activators deferrioxamine (DFO), CoCl2, V(SO4)2 and mimosine on collagen cleavage activity by collagenase in osteoarthritic (OA) articular cartilage explants. Materials and methods. 32 OA articular cartilages obtained after arthroplasty were examined in the study. Cartilages were cultured in the presence of 10-50μM DFO, CoCl2, V(SO4)2 or mimosine. Collagen cleavage activity was measured by ELISA. Inhibition of protein or DNA synthesis in the presence of [3H]-labeled proline or thymidine, respectively, was used for evaluation of examined agent toxicity. Results. Glycolysis activators DFO, CoCl2, V(SO4)2 or mimosine were capable of inhibiting type II collagen cleavage activity in OA articular cartilage explants. The examined agents have shown no toxic effect in the concentrations used. Conclusion. Glycolysis activation in articular chondrocytes may offer a means of inhibiting articular cartilage destruction in OA patients.

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