Thrombospondin 2 Promotes IL-6 Production in Osteoarthritis Synovial Fibroblasts via the PI3K/AKT/NF-κB Pathway

Hou, Chun‐Han; Tang, Chih‐Hsin; Chen, Po-Chun; Liu, Ju-Fang

doi:10.2147/jir.s314747

Cited by 11 publications

(8 citation statements)

References 66 publications

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“…The fact that TSP2 correlated with disease activity indicated that it retained a mechanism related to fibrosis as well as hepatic inflammation. Indeed, TSP2 is reportedly involved in inflammation during the pathogenesis of osteoarthritis by promoting interleukin-6 production in synovial fibroblasts via the PI3K/AKT/NF-κB pathway 23 . Future studies are needed to clarify the role of TSP2 in hepatitis pathogenesis.…”

Section: Discussionmentioning

confidence: 99%

Circulating thrombospondin 2 levels reflect fibrosis severity and disease activity in HCV-infected patients

Iwadare

Kimura

Tanaka

et al. 2022

Sci Rep

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Among several secreted glycoproteins belonging to the thrombospondin family, thrombospondin 2 (TSP2) is involved in various functions, including collagen/fibrin formation. Liver/serum TSP2 levels have been correlated to liver fibrosis stage and disease activity in nonalcoholic fatty liver disease. This study investigated whether serum TSP2 was associated with clinicopathological features in hepatitis C virus (HCV)-infected patients as well. A total of 350 patients with HCV who had undergone liver biopsy were retrospectively enrolled and divided into a discovery cohort (n = 270) and a validation cohort (n = 80). In the discovery cohort, serum TSP2 levels were moderately correlated with both liver fibrosis stage (r = 0.426, P < 0.0001) and activity grade (r = 0.435, P < 0.0001). The area under the receiver operating characteristic curve of TSP2 for predicting severe fibrosis (≥ F3) was 0.78 and comparable to or better than those of autotaxin (0.78), FIB-4 index (0.78), and APRI (0.76). The discovery cohort findings were closely replicated in the validation cohort. Moreover, comprehensive liver genetic analysis of HCV-infected patients confirmed that the expression of the THBS2 gene encoding TSP2 was significantly higher in severely fibrotic F4 than in F1 patients. Circulating TSP2 levels may reflect the severity of hepatic fibrosis/inflammation in HCV-infected patients.

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Section: Discussionmentioning

confidence: 99%

Circulating thrombospondin 2 levels reflect fibrosis severity and disease activity in HCV-infected patients

Iwadare

Kimura

Tanaka

et al. 2022

Sci Rep

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“…It is regarded as a protector in inflammatory diseases. Hou et al found that TSP-2 could protect cartilage destruction by promoting inflammatory factor in osteoarthritis patients [ 14 ]. A study carried on TSP-2 deficient mice, suggesting that TSP-2 could limit inflammatory cell infiltration during delayed-type hypersensitivity [ 15 ].…”

Section: Discussionmentioning

confidence: 99%

“…As an essential matricellular protein, TSP-2 plays a complicated role in some disease including inflammation, fibrosis, and malignances [12,13]. It is regarded as a protector in [14]. A study carried on TSP-2 deficient mice, suggesting that TSP-2 could limit inflammatory cell infiltration during delayed-type hypersen-sitivity [15].…”

Section: Discussionmentioning

confidence: 99%

Diagnostic and Prognostic Roles of Thrombospondin-2 in Digestive System Cancers

Gao

Chen

Zhao

et al. 2022

BioMed Research International

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Background. Cancers of digestive system have high case-fatality rate. It is important to find more appropriate methods in diagnosing and predicting gastrointestinal malignances. And thrombospondin-2 (TSP-2) was reported to have the functions, although results were not identical. So we performed this meta-analysis to clarify the significance of TSP-2 in this area. Methods. PubMed, Embase, Web of Science, Cochrane Library, and Clinicaltrial.gov were searched for relevant studies. Data were extracted from these involved records. For the meta-analysis of diagnostic test, bivariate mixed effect model was used to estimate diagnostic accuracy. For prognosis part, HRs and their 95% CIs were pooled to compare the overall survival (OS) and disease-free survival (DFS) between patients with high TSP-2 and low TSP-2. Results. Nine records were eligible for the analysis of diagnostic test. Pooled results were as follows: sensitivity 0.60 (0.52, 0.68), specificity 0.96 (0.91, 0.98), positive likelihood ratio (PLR) 15.4 (7.3, 32.2), negative likelihood ratio (NLR) 0.42 (0.34, 0.50), and diagnostic odds ratio (DOR) 37 (18, 76). While in prognosis part, 10 articles were included. Patients with increased TSP-2 had shorter OS ( HR = 1.64 , 95% CI = 1.21 -2.22); however, no difference was found in DFS between TSP-2 high and low groups ( HR = 1.44 , 95% CI = 0.28 -7.33). Conclusions. TSP-2, as a diagnostic marker, has a high specificity but a moderate sensitivity. Meanwhile, it plays a role in predicting OS. Therefore, making TSP-2 a routine assay could be beneficial to high-risk individuals and patients with digestive malignances.

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“…In addition, when coupled with IL-1, IL-6 increases the expression of MMP-1 and MMP-13 while decreasing the expression of collagen-II. 35 , 36 Another effective treatment for OA is COX-2 inhibition. 37 iNOS in chondrocytes synthesizes nitric oxide, which is a major inflammatory mediator in OA.…”

Section: Discussionmentioning

confidence: 99%

Madecassic Acid Ameliorates the Progression of Osteoarthritis: An in vitro and in vivo Study

Fu¹,

He²,

Wang³

et al. 2022

DDDT

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Purpose Osteoarthritis (OA) places a significant burden on society and finance, and there is presently no effective treatment besides late replacement surgery and symptomatic relief. The therapy of OA requires additional research. Madecassic acid (MA) is the first native triterpenoid compound extracted from Centella asiatica, which has a variety of anti-inflammatory effects. However, the role of MA in OA therapy has not been reported. This study aimed to explore whether MA could suppress the inflammatory response, preserve and restore chondrocyte functions, and ameliorate the progression of OA in vitro and in vivo. Methods Rat primary chondrocytes were treated with IL-1β to simulate inflammatory environmental conditions and OA in vitro. We examined the effects of MA at concentrations ranging from 0 to 200 µM on the viability of rat chondrocytes and selected 10 µM for further study. Using qRT-PCR, immunofluorescent, immunocytochemistry, and Western blotting techniques, we identified the potential molecular mechanisms and signaling pathways that are responsible for these effects. We established an OA rat model by anterior cruciate ligament transection (ACLT). The animals were then periodically injected with MA into the knee articular cavity. Results We found that MA could down-regulate the IL-1β-induced up-regulation of COX-2, iNOS and IL-6 and restore the cytoskeletal integrity of chondrocytes treated with IL-1β. Moreover, MA protects chondrocytes from IL-1β-induced ECM degradation by upregulating ECM synthesis related protein expression, including collagen-II and ACAN, and further down-regulating ECM catabolic related protein expression, including MMP-3 and MMP-13. Furthermore, we found that NF-κB/IκBα and PI3K/AKT signaling pathways were involved in the regulatory effects of MA on the inflammation inhibition and promotion of ECM anabolism on IL-1β-induced chondrocytes. Conclusion These findings suggest that MA appears to be a potentially small molecular drug for rat OA.

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Thrombospondin 2 Promotes IL-6 Production in Osteoarthritis Synovial Fibroblasts via the PI3K/AKT/NF-κB Pathway

Cited by 11 publications

References 66 publications

Circulating thrombospondin 2 levels reflect fibrosis severity and disease activity in HCV-infected patients

Circulating thrombospondin 2 levels reflect fibrosis severity and disease activity in HCV-infected patients

Diagnostic and Prognostic Roles of Thrombospondin-2 in Digestive System Cancers

Madecassic Acid Ameliorates the Progression of Osteoarthritis: An in vitro and in vivo Study

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