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.

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.

Detection of MMP-13 Activity on Intentionally Strain-Released Type-II Collagen Network in Bovine Articular Cartilage

2011 ◽  
Author(s):  
Nazli Caner ◽  
Jeffrey W. Ruberti
Keyword(s):  
Articular Cartilage ◽  
Degradation Kinetics ◽  
Type Ii Collagen ◽  
Healthy Tissue ◽  
Cartilage Explants ◽  
Cartilage Tissue ◽  
Mechanical Stimuli ◽  
Type Ii ◽  
Collagen Network ◽  
Mechanical Tension

Articular cartilage is a specialized avascular connective tissue found at the contact regions of diarthrodial joints. Cartilage has few cells (< 5% of the volume), though these cells can maintain the balance of turnover in healthy tissue, when the tissue is damaged, they are not able to repair the defects [1–3]. Extra cellular matrix (ECM) in cartilage comprises water, collagen (principally type II), proteoglycans and noncollagenous proteins. The type II collagen network, which is the dominant structural protein in cartilage ECM, constrains the expansion of the resident PGs and is generally held in mechanical tension. In osteoarthritis (OA), the balance of cartilage tissue production/degradation is thought to be affected by abnormal mechanical stimuli leading to net matrix resorption through production of excess degradative enzymes (e.g. matrix metalloproteinases (MMP) and aggrecanases) [4–8]. In OA tissue the amount of MMP-13 is thought to be increased relative to healthy tissue. OA typically occurs in older adults where, as cartilage ages, there is a marked decrease in the fixed charge density (FCD), the hydration and, consequently, mechanical tension on the collagen type II network [9–11]. We have hypothesized that loss of tension on the collagen network accelerates degradation by MMP. Detection of the effect of MMP on loaded, native cartilage could lead to insight about cartilage degradation kinetics in OA. However, it is quite difficult to controllably deliver MMP to cartilage, to activate the MMP during detensioning of the collagen network and to detect the effect on the cartilage mechanics (because cost limits the amount of MMP used). We have developed a transpirational enzyme loading method which is capable of precisely dosing bovine cartilage explants with a small, known quantity of MMP-13. Following enzyme insertion, we are able to detect the activity of the MMP on osmotically compressed cartilage (i.e. cartilage with a detensioned collagen network) via a simple hydration measurement.

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.

Parathyroid hormone-related protein (PTHrP) action in rat articular chondrocytes: comparison of PTH(1–34), PTHrP(1–34), PTHrP(1–141), PTHrP(100–114) and antisense oligonucleotides against PTHrP

1996 ◽  
Vol 150 (3) ◽  
pp. 359-368 ◽  
Author(s):  
T Tsukazaki ◽  
A Ohtsuru ◽  
H Namba ◽  
J Oda ◽  
K Motomura ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Dna Synthesis ◽  
Antisense Oligonucleotides ◽  
Articular Chondrocytes ◽  
Type Ii Collagen ◽  
Type Ii ◽  
Related Protein ◽  
Collagen Mrna ◽  
Parathyroid Hormone Related Protein ◽  
Significant Difference

Abstract Parathyroid hormone-related protein (PTHrP) is thought to be an important autocrine/paracrine factor for chondrocyte metabolism since mice lacking the PTHrP gene exhibit abnormal cartilage development. To determine the biological role of PTHrP in chondrocytes, we first compared the agonist potency of human (h) PTHrP(1–34) with hPTH(1–34) in cultured rat articular chondrocytes. Neither hPTHrP(1–34) nor hPTH(1–34) altered basal DNA synthesis, but attenuated the stimulatory effect of transforming growth factor β (TGF-β). Both agents suppressed the expression of α(1) type II collagen mRNA in a dose–response fashion with the same potency. In addition, the action of exogenously added hPTHrP(1–34) and hPTH(1–34) on intracellular cAMP and [Ca2+]i levels was similar. We next compared the effect of PTHrP within its entire amino acid sequence (1–141). With regard to thymidine incorporation, α(1) type II collagen gene expression and accumulation of cAMP and [Ca2+]i level, there was no significant difference between hPTHrP(1–34) and hPTHrP(1–141). PTHrP C-terminal (100–114) did not show any function. To further investigate PTHrP function, intracellular PTHrP translation was inhibited by a transgene of antisense oligonucleotides against PTHrP. Antisense oligonucleotides decreased PTHrP mRNA translation, specifically inhibited DNA synthesis in control as well as TGF-β-treated chondrocytes and enhanced α(1) type II collagen mRNA expression in TGF-β-treated chondrocytes. These results suggest that there is no significant difference between exogenously added hPTH(1–34), hPTHrP(1–34) and PTHrP(1–141) with regard to the biological action of these agents, including cell growth, differentiation and second messenger pathway. However, the result of DNA synthesis in the antisense PTHrP-inhibition study suggests that intracellular PTHrP may have an as yet unknown biological role, in addition to a classical PTH/PTHrP receptor-mediated function in the rat articular chondrocyte. Journal of Endocrinology (1996) 150, 359–368

scholarly journals Intermittent Dynamic Compression Confers Anabolic Effects in Articular Cartilage

2021 ◽  
Vol 11 (16) ◽  
pp. 7469
Author(s):  
Amalie Engstrøm ◽  
Frederik S. Gillesberg ◽  
Solveig S. Groen ◽  
Peder Frederiksen ◽  
Anne-Christine Bay-Jensen ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Mechanical Loading ◽  
Kinase Inhibitor ◽  
Dynamic Compression ◽  
Compressive Loading ◽  
Type Ii Collagen ◽  
Cartilage Explants ◽  
Type Ii ◽  
Bovine Articular Cartilage ◽  
Collagen Formation

(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.

scholarly journals Boosting the Intra-Articular Efficacy of Low Dose Corticosteroid through a Biopolymeric Matrix: An In Vivo Model of Osteoarthritis

Cells ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 1571
Author(s):  
Matilde Tschon ◽  
Francesca Salamanna ◽  
Lucia Martini ◽  
Gianluca Giavaresi ◽  
Luca Lorenzini ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Pain Sensitivity ◽  
Type Ii Collagen ◽  
Male Rats ◽  
In Vivo Model ◽  
Type Ii ◽  
Chemical Induction ◽  
Local Pain ◽  
Gait Parameters

The purpose of this study was to verify the efficacy of a single intra-articular (i.a.) injection of a hyaluronic acid-chitlac (HY-CTL) enriched with two low dosages of triamcinolone acetonide (TA, 2.0 mg/mL and 4.5 mg/mL), in comparison with HY-CTL alone, with a clinical control (TA 40 mg/mL) and with saline solution (NaCl) in an in vivo osteoarthritis (OA) model. Seven days after chemical induction of OA, 80 Sprague Dawley male rats were grouped into five arms (n = 16) and received a single i.a. injection of: 40 mg/mL TA, HY-CTL alone, HY-CTL with 2.0 mg/mL TA (RV2), HY-CTL with 4.5 mg/mL TA (RV4.5) and 0.9% NaCl. Pain sensitivity and Catwalk were performed at baseline and at 7, 14 and 21 days after the i.a. treatments. The histopathology of the joint, meniscus and synovial reaction, type II collagen expression and aggrecan expression were assessed 21 days after treatments. RV4.5 improved the local pain sensitivity in comparison with TA and NaCl. RV4.5 and TA exerted similar beneficial effects in all gait parameters. Histopathological analyses, measured by Osteoarthritis Research Society International (OARSI) and Kumar scores and by immunohistochemistry, evidenced that RV4.5 and TA reduced OA features in the same manner and showed a stronger type II collagen and aggrecan expression; both treatments reduced synovitis, as measured by Krenn score and, at the meniscus level, RV4.5 improved degenerative signs as evaluated by Pauli score. TA or RV4.5 treatments limited the local articular cartilage deterioration in knee OA with an improvement of the physical structure of articular cartilage, gait parameters, the sensitivity to local pain and a reduction of the synovial inflammation.

Finite Element Modeling of Osmotic Swelling in Tissue-Engineered Cartilage

2008 ◽  
Author(s):  
Liming Bian ◽  
Terri Ann N. Kelly ◽  
Eric G. Lima ◽  
Gerard A. Ateshian ◽  
Clark T. Hung
Keyword(s):  
Articular Cartilage ◽  
Potential Role ◽  
Swelling Pressure ◽  
Type Ii Collagen ◽  
Type Ii ◽  
Osmotic Swelling ◽  
Fixed Charges ◽  
Central Regions ◽  
Significant Research ◽  
Engineered Cartilage

Proteoglycans and Type II collagen represent the two major biochemical constituents of articular cartilage. Collagen fibrils in cartilage resist the swelling pressure that arises from the fixed charges of the glycosaminoglycans (GAGs), and together they give rise to the tissue’s unique load bearing properties. As articular cartilage exhibits a poor intrinsic healing capacity, there is significant research in the development of cell-based therapies for cartilage repair. In some of our tissue engineering studies, we have observed a phenomenon where chondrocyte-seeded hydrogel constructs display cracking in their central regions after significant GAG content has been elaborated in culture. A theoretical analysis was performed to gain greater insights into the potential role that the spatial distribution of proteoglycan and collagen may play in this observed response.

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