Matrix Metalloproteinase-3 induces proteoglycan degradation in gouty arthritis model

Shi, Le; Liang, Tao; Yang, Fan; Zhu, Fangfang; Liu, Jin; Jiang, Jia‐Qian; Wu, Xiaowei; Chen, An-Sheng; Yuan, Dongping; Liang, Xin-Li

doi:10.1016/j.gene.2020.145120

Cited by 11 publications

(5 citation statements)

References 31 publications

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“… 24 Studies have confirmed that traditional Chinese medicine can further affect the deposition of MSU crystals by inhibiting the degradation of proteoglycans. 25 Crystal preparation was done according to the method described by Coderre, 26 , 27 with some adjustments. All reagents were prepared under pyrogen-free conditions.…”

Section: Methodsmentioning

confidence: 99%

Tongbixiao Pills Improve Gout by Reducing Uric Acid Levels and Inhibiting Inflammation

ZhiguoShao

et al. 2022

Dose-Response

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Gout is a chronic disease. Gout symptoms are often experienced in the middle of the night. The onset of gout in the middle of the night is closely related to abnormal liver and gallbladder meridian. The purpose of this study was to investigate the clinical efficacy and possible mechanism of action of Tongbixiao pills in the treatment of hyperuricemia and gouty arthritis. The Tongbixiao pills we used included several traditional Chinese medicines, most of which tonify the spleen; strengthen the liver; benefit the kidney; and reduce heat, dampness, and blood stasis. In this randomized clinical study of 105 patients, we found that Tongbixiao pills can reduce uric acid levels in hyperuricemia patients. Additionally, the efficacy was similar to that of allopurinol and the level of uric acid did not increase significantly at eight weeks after withdrawal. In the absence of notable adverse reactions, Tongbixiao pills can also increase uric acid excretion, reduce serum creatinine and lipid levels, and reduce inflammation and relieve gout symptoms. In addition, we used SD rats to simulate gout and arthritis and divided them into five groups: normal group, model group, low-dose group, medium-dose group, and high-dose group. The inflammatory indices of the 40 SD rats were observed. After seven days, ankle swelling in rats in the treatment group was significantly reduced. The indices of uric acid, creatinine, and urea nitrogen in the treatment group were significantly lower than those in the model group, which proved that Tongbixiao pills could inhibit hyperuricemia in rats, thus treating gout. This study demonstrates that Tongbixiao pills can treat gout, provide more treatment options for gouty arthritis, and improve the quality of life of patients.

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Section: Methodsmentioning

confidence: 99%

Tongbixiao Pills Improve Gout by Reducing Uric Acid Levels and Inhibiting Inflammation

ZhiguoShao

et al. 2022

Dose-Response

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“…In this study, MMP3 and MMP13 were signi cantly suppressed by Vangl2 silencing. These two MMPs are major contributors to the degenerative process in OA due to their digestion of Col-2 [25,26]. Moreover, MMP9, the main enzyme degrading aggrecan and collagen hydrolysate, decreased to the level of control group in Vangl2-silencing chondrocyte.…”

Section: Discussionmentioning

confidence: 95%

Silencing of Vangl2 Attenuates the Inflammation Promoted by Wnt5a via MAPK and NF-κB Pathway in Chondrocytes.

Zhang

et al. 2020

Preprint

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Background: The Wnt planar cell polarity (PCP) pathway is implicated in osteoarthritis (OA) both in animals and in humans. Van Gogh-like 2 (Vangl2) is a key PCP protein that is required for the orientation and alignment of chondrocytes in the growth plate. However, its functional roles in OA still remain undefined. Here, we explored the effects of Vangl2 on OA chondrocyte in vitro, and further elucidated the molecular mechanism of silencing Vangl2 in Wnt5a-overexpressing OA chondrocytes.Methods: Chondrocytes were treated with IL-1β (10 ng/mL) to simulate the inflammatory microenvironment of OA. The expression levels of Vangl2, Wnt5a, MMPs, and related proinflammatory cytokines were measured by RT-qPCR. Small interfering RNA (siRNA) of Vangl2 and the plasmid targeting Wnt5a were constructed and transfected into ATDC5 cells. Then the functional roles of silencing Vangl2 in the OA chondrocytes were investigated by Western blotting, RT-qPCR, and immunocytochemistry (ICC). Transfected OA chondrocytes were subjected to Western blotting to analyze the relationship between Vangl2 and related signaling pathways. Results: IL-1β induced the production of Vangl2, Wnt5a and MMPs in a time-dependent manner and the significantly increased expression of Vangl2. Vangl2 silencing effectively suppressed the expression of MMP3, MMP9, MMP13 and IL-6 at both gene and protein levels, and upregulated the expression of type II collagen and aggrecan. Moreover, knockdown of Vangl2 inhibited the phosphorylation of MAPK signaling molecules (P38, ERK, and JNK) and P65 in Wnt5a-overexpressing OA chondrocytes.Conclusions: For the first time, we demonstrate that Vangl2 is involved in the OA process. Vangl2 silencing can notably alleviate OA progression in vitro by inhibiting the expression of MMPs and increasing the formation of the cartilage matrix, and can inhibit the proinflammatory effects of Wnt5a via MAPK and NF-κB pathway. This study provides new insight into the mechanism of cartilage inflammation.

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“…It is also produced by membrane synovium cells. MMP-3 is also known as stromelysin-1 and is responsible for the destruction of ECM in the cartilage, especially proteoglycans (PGs) [ 46 ]. MMP-13 is known as collagenase 3 and responsible for the degradation of type II, IV, and IX collagen as well as proteoglycans in cartilage [ 47 ].…”

Section: Discussionmentioning

confidence: 99%

Seahorse Protein Hydrolysate Ameliorates Proinflammatory Mediators and Cartilage Degradation on Posttraumatic Osteoarthritis with an Obesity Rat Model

Sudirman

Tseng

Chen

et al. 2022

BioMed Research International

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Osteoarthritis (OA) is one of the age-related diseases and is highly present on the knees. Obesity and mechanical injuries as a risk factor of OA are attributed to cartilage disintegration, joint loading, and inflammation. This study is aimed at investigating the effects of seahorse protein hydrolysate (SH) on posttraumatic osteoarthritis in an obesity rat. The OA model was developed by anterior cruciate ligament transection with medial meniscectomy in a high-fat diet- (HFD-) induced obesity rat model. The male Sprague-Dawley rats were fed a HFD for 6 weeks before OA surgery. The OA rats were treated with oral gavage by 4, 8, or 20 mg/kg of body weight of SH for 6 weeks of treatment. The expressions of plasma proinflammatory factors, C-telopeptide of type II collagen, and matrix metalloproteinase- (MMP-) 3 and MMP-13 were reduced by SH treatment. Plasma superoxide dismutase and glutathione peroxidase activities were enhanced by SH. SH also relieved the pain of the knee joint and swelling as well as decreased proteoglycan loss in the knee articular cartilage caused by osteoarthritis. Based on these results, SH suppressed proinflammatory factors and attenuated cartilage degradation and pain in the OA model. Therefore, seahorse protein hydrolysate might be a potential opportunity for improving the development of osteoarthritis.

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Matrix Metalloproteinase-3 induces proteoglycan degradation in gouty arthritis model

Cited by 11 publications

References 31 publications

Tongbixiao Pills Improve Gout by Reducing Uric Acid Levels and Inhibiting Inflammation

Tongbixiao Pills Improve Gout by Reducing Uric Acid Levels and Inhibiting Inflammation

Silencing of Vangl2 Attenuates the Inflammation Promoted by Wnt5a via MAPK and NF-κB Pathway in Chondrocytes.

Seahorse Protein Hydrolysate Ameliorates Proinflammatory Mediators and Cartilage Degradation on Posttraumatic Osteoarthritis with an Obesity Rat Model

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