scholarly journals Delay in articular cartilage degeneration of the knee joint by the conditional removal of discoidin domain receptor 2 in a spontaneous mouse model of osteoarthritis

2020 ◽  
Vol 8 (18) ◽  
pp. 1178-1178
Author(s):  
Xiaolong Li ◽  
Yi Chen ◽  
Rui Xu ◽  
Yan Wang ◽  
Fan Jian ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Mouse Model ◽  
Knee Joint ◽  
Cartilage Degeneration ◽  
Discoidin Domain Receptor ◽  
Discoidin Domain Receptor 2 ◽  
Articular Cartilage Degeneration

scholarly journals Intact Pericellular Matrix of Articular Cartilage Is Required for Unactivated Discoidin Domain Receptor 2 in the Mouse Model

2011 ◽  
Vol 179 (3) ◽  
pp. 1338-1346 ◽  
Author(s):  
Lin Xu ◽  
Ilona Polur ◽  
Jacqueline M. Servais ◽  
Sirena Hsieh ◽  
Peter L. Lee ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Mouse Model ◽  
Pericellular Matrix ◽  
Discoidin Domain Receptor ◽  
Discoidin Domain Receptor 2

TNIIIA2, The Peptide of Tenascin-C, as a Candidate for Preventing Articular Cartilage Degeneration

Cartilage ◽  
2020 ◽  
pp. 194760352091230 ◽  
Author(s):  
Tetsuya Hattori ◽  
Masahiro Hasegawa ◽  
Hironori Unno ◽  
Takahiro Iino ◽  
Fumio Fukai ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Knee Joint ◽  
Cartilage Degeneration ◽  
Group Iv ◽  
Control Group ◽  
Tenascin C ◽  
Group I ◽  
Group Ii ◽  
Phosphate Buffered Saline ◽  
Articular Cartilage Degeneration

Objective TNIIIA2 is a peptide of the extracellular matrix glycoprotein tenascin-C. We evaluated whether intra-articular injection of TNIIIA2 could prevent articular cartilage degeneration without inducing synovitis in an osteoarthritis mice model. Design Ten micrograms per milliliter of TNIIIA2 were injected into the knee joint of mice (group II) to evaluate the induction of synovitis. The control group received an injection of phosphate buffered saline (group I). Synovitis was evaluated using synovitis score 2 and 4 weeks after injection. The ligaments of knee joints of mice were transected to make the osteoarthritis model. After transection, 10 µg/mL of TNIIIA2 was injected into the knee joint (group IV). The control group received an injection of phosphate buffered saline after transection (group III). Histologic examinations were made using hematoxylin and eosin and safranin-O staining at 2, 4, 8, and 12 weeks postoperatively. An in vitro study was also performed to determine the mechanism by which TNIIIA2 prevents cartilage degeneration. Human chondrocytes were isolated, cultured, and treated with TNIIIA2. The expressions of various mRNAs, including inflammatory cytokines, and anabolic and catabolic factors for cartilage were compared using real-time polymerase chain reaction. Results There were no differences between groups in the study of intra-articular injection of mice (group I vs. group II). In the osteoarthritis model, we found development of osteoarthritis was suppressed in group IV at 4 and 8 weeks. TNIIIA2 upregulated the expressions of tumor necrosis factor-α, matrix metalloproteinase 3, and basic fibroblast growth factor. Conclusion We demonstrated that TNIIIA2 could prevent cartilage degeneration without synovitis.

scholarly journals Attenuation of the Progression of Articular Cartilage Degeneration by Inhibition of TGF-β1 Signaling in a Mouse Model of Osteoarthritis

2015 ◽  
Vol 185 (11) ◽  
pp. 2875-2885 ◽  
Author(s):  
Rebecca Chen ◽  
Michelle Mian ◽  
Martin Fu ◽  
Jing Ying Zhao ◽  
Liang Yang ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Mouse Model ◽  
Cartilage Degeneration ◽  
Articular Cartilage Degeneration ◽  
Tgf Β1

The Effect of Total Meniscectomy versus Caudal Pole Hemimeniscectomy on the Stifle Joint of the Sheep

1999 ◽  
Vol 12 (02) ◽  
pp. 56-63 ◽  
Author(s):  
C. R. Bellenger ◽  
P. Ghosh ◽  
Y. Numata ◽  
C. Little ◽  
D. S. Simpson
Keyword(s):  
Tissue Culture ◽  
Articular Cartilage ◽  
Fibrous Tissue ◽  
Cartilage Degeneration ◽  
Medial Compartment ◽  
Proteoglycan Synthesis ◽  
Stifle Joint ◽  
Medial Meniscectomy ◽  
Tibial Condyle ◽  
Articular Cartilage Degeneration

SummaryTotal medial meniscectomy and caudal pole hemimeniscectomy were performed on the stifle joints of twelve sheep. The two forms of meniscectomy produced a comparable degree of postoperative lameness that resolved within two weeks of the operations. After six months the sheep were euthanatised and the stifle joints examined. Fibrous tissue that replaced the excised meniscus in the total meniscectomy group did not cover as much of the medial tibial condyle as the residual cranial pole and caudal fibrous tissue observed following hemimeniscectomy. The articular cartilage from different regions within the joints was examined for gross and histological evidence of degeneration. Analyses of the articular cartilage for water content, glycosaminoglycan composition and DNA content were performed. The proteoglycan synthesis and release from explanted articular cartilage samples in tissue culture were also measured. There were significant pathological changes in the medial compartment of all meniscectomised joints. The degree of articular cartilage degeneration that was observed following total meniscectomy and caudal pole meniscectomy was similar. Caudal pole hemimeniscectomy, involving transection of the meniscus, causes the same degree of degeneration of the stifle joint that occurs following total meniscectomy.The effect of total medial meniscectomy versus caudal pole hemimeniscectomy on the stifle joint of sheep was studied experimentally. Six months after the operations gross pathology, histopathology, cartilage biochemical analysis and the rate of proteoglycan synthesis in tissue culture were used to compare the articular cartilage harvested from the meniscectomised joints. Degeneration of the articular cartilage from the medial compartment of the joints was present in both of the groups. Caudal pole hemimeniscectomy induces a comparable degree of articular cartilage degeneration to total medial meniscectomy in the sheep stifle joint.

MOLECULAR CONTROL OF ARTICULAR CARTILAGE DEGENERATION BY TRANSFORMING GROWTH FACTOR ALPHA

2008 ◽  
Vol 31 (4) ◽  
pp. 2
Author(s):  
Tom Appleton ◽  
Shirine Usmani ◽  
John Mort ◽  
Frank Beier
Keyword(s):  
Gene Expression ◽  
Articular Cartilage ◽  
Growth Factor ◽  
P38 Mapk ◽  
Transforming Growth Factor ◽  
Cartilage Degeneration ◽  
Signalling Pathways ◽  
Transforming Growth Factor Alpha ◽  
Factor Alpha ◽  
Articular Cartilage Degeneration

Background: Articular cartilage degeneration is a hallmark of osteoarthritis (OA). We previously identified increased expression of transforming growth factor alpha (TGF?) and chemokine (C-C motif) ligand 2 (CCL2) in articular cartilage from a rat modelof OA (1,2). We subsequently reported that TGF? signalling modified chondrocyte cytoskeletal organization, increased catabolic and decreased anabolic gene expression and suppressed Sox9. Due to other roles in chondrocytes, we hypothesized that the effects ofTGF? on chondrocytes are mediated by Rho/ROCK and MEK/ERK signaling pathways. Methods: Primary cultures of chondrocytes and articularosteochondral explants were treated with pharmacological inhibitors of MEK1/2(U0126), ROCK (Y27632), Rho (C3), p38 MAPK (SB202190) and PI3K (LY294002) to elucidate pathway involvement. Results: Using G-LISA we determined that stimulation of primary chondrocytes with TGF? activates RhoA. Reciprocally, inhibition of RhoA/ROCK but not other signalling pathways prevents modification of the actin cytoskeleton in responseto TGF?. Inhibition of MEK/ERKsignaling rescued suppression of anabolic gene expression by TGF? including SOX9 mRNA and protein levels. Inhibition of MEK/ERK, Rho/ROCK, p38 MAPK and PI3K signalling pathways differentially controlled the induction of MMP13 and TNF? gene expression. TGF? also induced expression of CCL2 specifically through MEK/ERK activation. In turn, CCL2 treatment induced the expression of MMP3 and TNF?. Finally, we assessed cartilage degradation by immunohistochemical detection of type II collagen cleavage fragments generated by MMPs. Blockade of RhoA/ROCK and MEK/ERK signalling pathways reduced the generation of type IIcollagen cleavage fragments in response to TGF? stimulation. Conclusions: Rho/ROCK signalling mediates TGF?-induced changes inchondrocyte morphology, while MEK/ERK signalling mediates the suppression ofSox9 and its target genes, and CCL2 expression. CCL2, in turn, induces the expression of MMP3 and TNF?, two potent catabolic factors known to be involved in OA. These pathways may represent strategic targets for interventional approaches to treating cartilage degeneration in osteoarthritis. References: 1. Appleton CTG et al. Arthritis Rheum 2007;56:1854-68. 2. Appleton CTG et al. Arthritis Rheum 2007; 56:3693-705.

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