AMD3100 Attenuates Matrix Metalloprotease-3 and -9 Expressions and Prevents Cartilage Degradation in a Monosodium Iodo-Acetate–Induced Rat Model of Temporomandibular Osteoarthritis

Wang, Xiaoyan; Chen, Yan; Tang, Xuejiao; Jiang, Linhong; Ji, Ping

doi:10.1016/j.joms.2015.12.018

Cited by 19 publications

(20 citation statements)

References 45 publications

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“…Although the aetiological mechanisms of OA remain unclear, studies suggest that the SDF-1/CXCR4 signaling pathway plays a vital role in its development[6,7,16,17]. In the knee, SDF-1 is produced by the synovium and secreted into the joint cavity and blood, however, its receptor CXCR4 is expressed on chondrocytes in the joint.…”

Section: Discussionmentioning

confidence: 99%

“…Recently it was shown that the SDF- 1/CXCR4 signaling pathway plays a key role in the pathogenesis of cartilage degeneration[6,7]. In OA, synovial cells in joints synthesize and secrete stromal cell derived factor-1 (SDF-1) into the synovial fluid[8] and chondrocytes in cartilage tissue express chemokine receptor 4 (CXCR4)–a major receptor of SDF-1.…”

Section: Introductionmentioning

confidence: 99%

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T140 blocks the SDF-1/CXCR4 signaling pathway and prevents cartilage degeneration in an osteoarthritis disease model

et al. 2017

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Osteoarthritis (OA) is one of the most common diseases affecting older people; however, there remains no effective targeted drug to combat OA. The aims of this study were (1) to explore the effect of T140 in regulating degeneration of articular cartilage in vivo by targeted blocking of the SDF-1/CXCR4 signaling pathway, and (2) to provide experimental evidence for the development of a novel OA-targeted pharmacotherapy. Thirty-six healthy Hartley guinea pigs were randomly divided into three groups: a T140-treated group (n = 12), a phosphate buffer saline control group (n = 12) and an untreated control group (n = 12). At 2, 4, 6, 8, 10 and 12 weeks of treatment, SDF-1 in serum was quantified by enzyme-linked immunosorbent assay. At 12 weeks of treatment, the cartilage from knee tibial plateau in the knee joint was collected for H&E, Safranin-O staining and Mankin grading; measurement for mRNA levels of matrix metalloproteinases (MMP-3, MMP-9 and MMP-13), aggrecan (ACAN) and collagen II (Col II) using RT-PCR; and measurement for Col II protein levels by western blot. Results showed that SDF-1 in serum increased in the T140 group and increased in the control groups. H&E and Safranin-O staining revealed less cartilage loss in T140-treated animals compared to controls. The mRNA levels of MMP-3, MMP-9 and MMP-13 in cartilage were much lower in the T140 group than other groups, but mRNA levels of ACAN and Col II in cartilage were higher in the T140-treated group. Col II protein levels in the T140 group and control groups were different. T140 can downregulate the expression of matrix-degrading enzyme and lessen the degeneration of cartilage by blocking the SDF-1/CRCR4 signaling pathway in vivo. This mechanism may present a pharmacological target for the treatment of OA.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

T140 blocks the SDF-1/CXCR4 signaling pathway and prevents cartilage degeneration in an osteoarthritis disease model

et al. 2017

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“…The early blood vessels of OA from subchondral bone can be invaded into the calcified cartilage and can gradually spread to the cartilage of the superficial layer with the progression of the disease. The blood vessel invasion can destroy the integrity of the boundary of articular cartilage and subchondral bone, the vascular endothelial cells can secrete a variety of factors simultaneously, thereby regulating the growth and metabolism of cartilage cells and may directly involve in the degradation of cartilage matrix (6). It has been believed that the thinning of OA articular cartilages is not only associated with the degeneration of the cartilage tissue itself, but also associated with the bone formation in the cartilage proceeded continuously at the boundary of bone and cartilage, while the angiogenesis is an important condition for endochondral bone formation and osteophyte formation (7).…”

Section: Discussionmentioning

confidence: 99%

Significance of new blood vessels in the pathogenesis of temporomandibular joint osteoarthritis

Liu¹,

Dai²,

Wang³

et al. 2017

Experimental and Therapeutic Medicine

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We studied the significance of new blood vessels in the pathogenesis of temporomandibular joint osteoarthritis (TMJOA). Fifteen 8-week-old female Sprague-Dawley rats were selected to establish TMJOA models of gradually induced occlusal disorders. Five rats were sacrificed at 4, 8 and 16 weeks, and histological exam was conducted along with micro-computed tomography observation on the condyle specimen. The distribution and number of new blood vessels breaking were observed through the tidemark through CD34 immunofluorescence staining. The proliferation of chondrocytes were detected through Ki67 immunohistochemical staining, and the differentiation functions of chondrocytes were observed through PTHrP and IHH immunohistochemical staining. The degradation functions of cartilage matrix were observed through matrix metalloproteinase (MMP)-9 immunohistochemical staining to detect the expression of vascular growth promotion and inhibition factors with vascular endothelial growth factor (VEGF), CTGF and CHM-1 immunohistochemical staining and screen differentially expressed genes through gene chip analysis method. It was found that the condyle tissue full thickness, fiber layer thickness and calcified cartilage layer thickness were significantly increased with time (P<0.05). Bone mineral density, trabecular thickness and Tb.Sp were also increased significantly with time, BS/BV and trabecular number were decreased significantly with time (P<0.05). The new blood vessels reached the deep layer of calcified cartilage until the tide line was broken and non-calcified cartilage was invaded. The number of vessels were increased significantly with time (P<0.05). Ki67, PTHrP and IHH-positive rates were increased significantly (P<0.05). MMP-9, VEGF, CTGF and CHM-1 were increased significantly (P<0.05). VEGF, CTGF and CHM-1 mRNA were upregulated differentially with the expressed genes. In conclusion, the new blood vessels may be important in the pathogenesis of TMJOA.

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“…Wang et al indicated that Celastrol treatment attenuated joint pain and cartilage damage in OA rats by suppression of the SDF-1/CXCR4 pathway [11]. Moreover, SDF-1-induced cartilage degradation and Matrix Metalloprotease-3 (MMP-3) and MMP-9 expressions can be attenuated by the administration of CXCR4 antagonists like TN14003 and AMD3100 in vivo [12,13].…”

Section: Introductionmentioning

confidence: 99%

miR-142-5p as a CXCR4-Targeted MicroRNA Attenuates SDF-1-Induced Chondrocyte Apoptosis and Cartilage Degradation via Inactivating MAPK Signaling Pathway

Xiang

Liu

Yang

et al. 2020

Biochemistry Research International

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Osteoarthritis (OA) is a chronic joint function disorder with characteristics of chondrocytes reduction and extracellular matrix (ECM) components destruction. MicroRNAs (miRNAs) and the SDF-1/CXCR4 axis are essential factors of chondrocyte apoptosis and ECM degeneration. However, very few studies have investigated the correlation between miRNAs and the SDF-1/CXCR4 axis in osteoarthritis so far. Here, through miRNAs microarray and bioinformatics analyses, we identified miR-142-5p as a CXCR4-targeted and dramatically downregulated miRNA in cartilage from OA patients, as well as in SDF-1-induced OA chondrocytes in vitro. In SDF-1-treated primary human OA chondrocytes that were transfected with a miR-142-5p mimic or inhibitor, the expression of CXCR4 was found to be inversely correlated with the expression of miR-142-5p. The dual luciferase reporter assay further verified the target relationship between miR-142-5p and CXCR4. Overexpression of miR-142-5p alleviated OA pathology by suppressing chondrocyte apoptosis, even in CXCR4 overexpressed OA chondrocytes. This was associated with decreased cartilage matrix degradation, reduced cartilage inflammation, and inactivated MAPK signaling pathway. Our study suggests that upregulated expression of CXCR4-targeted miR-142-5p can inhibit apoptosis, inflammation, and matrix catabolism and inactivate the MAPK signaling pathway in OA chondrocytes. Our work provides important insight into targeting miR-142-5p and the SDF-1/CXCR4 axis in OA therapy.

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AMD3100 Attenuates Matrix Metalloprotease-3 and -9 Expressions and Prevents Cartilage Degradation in a Monosodium Iodo-Acetate–Induced Rat Model of Temporomandibular Osteoarthritis

Cited by 19 publications

References 45 publications

T140 blocks the SDF-1/CXCR4 signaling pathway and prevents cartilage degeneration in an osteoarthritis disease model

T140 blocks the SDF-1/CXCR4 signaling pathway and prevents cartilage degeneration in an osteoarthritis disease model

Significance of new blood vessels in the pathogenesis of temporomandibular joint osteoarthritis

miR-142-5p as a CXCR4-Targeted MicroRNA Attenuates SDF-1-Induced Chondrocyte Apoptosis and Cartilage Degradation via Inactivating MAPK Signaling Pathway

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