The study of targeted blocking SDF-1/CXCR4 signaling pathway with three antagonists on MMPs, type II collagen, and aggrecan levels in articular cartilage of guinea pigs

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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Mir-149 Promotes Survival and Differentiation of Bone Marrow Mesenchymal Stem Cells by Regulating Interleukin-6/Signal Transducer and Activator of Transcription 3 Signaling Pathway

Journal of Biomaterials and Tissue Engineering ◽

10.1166/jbt.2019.2110 ◽

2019 ◽

Vol 9 (8) ◽

pp. 1160-1166

Author(s):

Guozhong Qin ◽

Shaochuan Huo ◽

Juehui Li ◽

Yin Lian ◽

Xiaoli Jin

Keyword(s):

Bone Marrow ◽

Signaling Pathway ◽

Caspase 3 ◽

Type Ii Collagen ◽

Type Ii ◽

Alp Activity ◽

Stat3 Signaling ◽

Stat3 Signaling Pathway ◽

Marrow Mesenchymal Stem Cells ◽

Sirna Group

Bone marrow mesenchymal stem cells (BMSCs) can self-renew with multi-directional differentiation. Mir-149 is involved in various diseases, but whether Mir-149 regulates the survival and differentiation of BMSCs and related mechanisms remains unclear. BMSCs were isolated and randomly divided into Si-NC group, Mir-149 siRNA group, and Mir-149 siRNA + STAT3 inhibitor WP1066 group followed by analysis of the expression of Mir-149, RUNX2 and OPN mRNA by real time PCR, BMSCs proliferation by MTT assay, Caspase 3 activity, ALP activity, formation of type II collagen and IL-6 level by ELISA, as well as STAT3 signaling pathway expression by Western blot. Mir-149 expression was reduced in BMSCs of Mir-149 siRNA group, with promoted survival of BMSCs, decreased Caspase 3 activity, increased expression of RUNX2 and OPN, type II collagen formation, ALP activity, IL-6 secretion, as well as elevated pSTAT3 phosphorylation. The differences were statistically significant compared to Si-NC group (P < 0.05). Mir-149 siRNA + WP1066 inhibited pSTAT3 phosphorylation, reduced BMSCs survival, increased Caspase 3 activity, decreased RUNX2 and OPN expression, type II collagen production, ALP activity, as well as reduced IL-6 secretion. Compared with Mir-149 siRNA group, there were significant differences (P < 0.05). Down-regulation of Mir-149 in BMSCs can promote BMSCs survival and osteogenic differentiation by regulating IL-6/STAT3 signaling pathway.

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