Identification of hydroxypyridinium crosslinking sites in type II collagen of bovine articular cartilage

(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.

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

Cells ◽

10.3390/cells9071571 ◽

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.

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Finite Element Modeling of Osmotic Swelling in Tissue-Engineered Cartilage

ASME 2008 Summer Bioengineering Conference, Parts A and B ◽

10.1115/sbc2008-192368 ◽

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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The Effects of Proteoglycan and Type II Collagen on T1ρ Relaxation Time of Articular Cartilage

Journal of the Korean Society of Radiology ◽

10.3348/jksr.2015.72.2.108 ◽

2015 ◽

Vol 72 (2) ◽

pp. 108

Author(s):

Won Seok Choi ◽

Hye Jin Yoo ◽

Sung Hwan Hong ◽

Ja-Young Choi

Keyword(s):

Relaxation Time ◽

Articular Cartilage ◽

Type Ii Collagen ◽

Type Ii

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Proteomic Analysis of Articular Cartilage Shows Increased Type II Collagen Synthesis in Osteoarthritis and Expression of Inhibin βA (Activin A), a Regulatory Molecule for Chondrocytes

Journal of Biological Chemistry ◽

10.1074/jbc.m407041200 ◽

2004 ◽

Vol 279 (42) ◽

pp. 43514-43521 ◽

Cited By ~ 114

Author(s):

Monika Hermansson ◽

Yasunobu Sawaji ◽

Mark Bolton ◽

Susan Alexander ◽

Andrew Wallace ◽

...

Keyword(s):

Articular Cartilage ◽

Proteomic Analysis ◽

Collagen Synthesis ◽

Type Ii Collagen ◽

Activin A ◽

Type Ii ◽

Regulatory Molecule

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Theory of the Short Time Mechanical Relaxation in Articular Cartilage

Journal of Biomechanical Engineering ◽

10.1115/1.4005174 ◽

2011 ◽

Vol 133 (10) ◽

Cited By ~ 3

Author(s):

J. W. Ruberti ◽

J. B. Sokoloff

Keyword(s):

Hyaluronic Acid ◽

Articular Cartilage ◽

Chondroitin Sulfate ◽

Relaxation Times ◽

Type Ii Collagen ◽

Mechanical Relaxation ◽

Side Chains ◽

Type Ii ◽

Interface Area ◽

Short Time

Articular cartilage is comprised of macromolecules, proteoglycans, with (charged) chondroitin sulfate side-chains attached to them. The proteoglycans are attached to longer hyaluronic acid chains, trapped within a network of type II collagen fibrils. As a consequence of their relatively long persistence lengths, the number of persistence lengths along the chondroitin sulfate and proteoglycan chains is relatively small, and consequently, the retraction times for these side chains are also quite short. We argue that, as a consequence of this, they will not significantly inhibit the reptation of the hyaluronic acid chains. Scaling arguments applied to this model allow us to show that the shortest of the mechanical relaxation times of cartilage, that have been determined by Fyhrie and Barone to be due to reptation of the hyaluronic acid polymers, should have a dependence on the load, i.e., force per unit interface area P, carried by the cartilage, proportional to P3/2.

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

The American Journal of Sports Medicine ◽

10.1177/0363546517741306 ◽

2017 ◽

Vol 46 (3) ◽

pp. 713-727 ◽

Cited By ~ 7

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.

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