Peng-Fei Hu

ERK and Akt signaling pathways are involved in advanced glycation end product-induced autophagy in rat vascular smooth muscle cells

Advanced glycation end products (AGEs) play an important role in the proliferation of vascular smooth muscle cells (VSMCs) and accelerate atherosclerosis in diabetic patients. Autophagy, a life-sustaining process, is stimulated in atherosclerotic plaques by oxidized lipids, inflammation and metabolic stress conditions. In our studies, we utilized MTT assays to show that autophagy is involved in AGE-induced proliferation of VSMCs. Furthermore, treatment with AGEs (100 μg/ml) could induce autophagy in a time- and dose-dependent manner in rat aortic VSMCs. These results were further substantiated by electron microscopy and immunofluorescence imaging. Treatment with AGEs activated ERK, JNK and p38/MAPK, but inhibited Akt. Pretreatment with an ERK inhibitor and an Akt activator inhibited AGE-induced autophagy, demonstrating that AGEs induce autophagy in VSMCs through the ERK and Akt signaling pathways. In addition, RNA interference of RAGE decreased autophagy, indicating that RAGE is pivotal in the process of AGE-induced autophagy. Therefore, AGE-induced autophagy contributes to the process of AGE-induced proliferation of VSMCs, which is related to atherosclerosis in diabetes.

The emerging role of adipokines in osteoarthritis: a narrative review

Osteoarthritis (OA) is a most common multifactorial degenerative joint disease in elderly individuals. OA is affecting severely the quality of life of patients, while the causes of OA are not completely understood. Age, obesity, the female sex, and previous injury are considered as significant risk factors. Recently, increased levels of adipokines which are mainly produced by adipocytes have been detected in patients with osteoarthritis. Moreover, studies on different adipokines all reveal that they have played proinflammatory and catabolic/anabolic roles during the pathophysiology of OA. In the present review, we summarize current data on the effect of the adipose tissue-derived hormones leptin, adiponectin, resistin and visfatin on initiation and progression of OA.

Increased serum concentrations of visfatin and its production by different joint tissues in patients with osteoarthritis

Abstract Background: The goal of this study was to investigate the distribution of visfatin in paired serum and synovial fluid (SF) samples from patients with osteoarthritis (OA), and in serum from healthy controls. In addition, we wished to determine the potential sources of visfatin in joint tissue. Methods: Twenty-three patients with OA requiring total knee arthroplasty (TKA), 17 healthy subjects and ten donors requiring amputation were included in the study. Concentrations of visfatin in serum and SF were analyzed using an enzyme-linked immunosorbent assay (ELISA). The concentration of visfatin was also measured in conditioned media from cultured joint tissues. Results: We found serum visfatin concentrations to be higher in patients with OA compared to healthy controls (p<0.05), and SF-visfatin concentrations exceeded those in paired serum (p=0.004). In addition, infrapatellar fat pad and synovium were important sources of visfatin, while osteophytes released largest amounts of visfatin. Therefore, osteophytes can be considered a major source of visfatin in the knee joint in patients with OA. Conclusions: These results suggest that visfatin may be involved in the pathophysiology of OA and may have local effects in the joint during the process of OA. Clin Chem Lab Med 2010;48:1141–5.

Anti-arthritic effects of chlorogenic acid in interleukin-1β-induced rabbit chondrocytes and a rabbit osteoarthritis model

Cartilage degradation is one of the pathological changes of osteoarthritis (OA), and accumulating evidence suggests an excess of matrix metalloproteinases (MMPs) plays a role in this cartilage breakdown. Here, we investigated the effects of chlorogenic acid (CGA) on the mRNA and protein expression of MMPs in interleukin (IL)-1β-induced rabbit chondrocytes and evaluated the in vivo effects of CGA in experimental OA induced by anterior cruciate ligament transection (ACLT) in rabbits. Using quantitative real-time PCR and ELISA to investigate the expression levels of MMP-1, MMP-3, MMP-13, and tissue inhibitors of metalloproteinase-1(TIMP-1) in IL-1β-induced rabbit chondrocytes, we showed that CGA inhibits the expression of these MMPs while increasing TIMP-1 expression, at both the mRNA and protein levels. In addition, IL-1β-induced activation of nuclear factor kappa B (NF-κB) and the degradation of inhibitor of κB (IκB)-α were suppressed by CGA. In rabbits, CGA decreased cartilage degradation as assessed by morphological and histological analyses. The down-regulation of MMP-1, MMP-3, and MMP-13 expression and up-regulation of TIMP-1 expression were also detected in CGA-treated cartilage compared with vehicle-treated cartilage, confirming these findings in an in vivo model. Taken together, these findings indicate that CGA may be considered as a possible candidate agent in the treatment of OA.

Morin inhibits interleukin-1β-induced nitric oxide and prostaglandin E2 production in human chondrocytes

It is well known that the inflammatory cytokines play important roles in osteoarthritis (OA). In the present study, we investigated the anti-inflammatory properties of morin in chondrocytes. The nitric oxide (NO) production was determined by Griess method, the prostaglandin E2 (PGE(2)) production was detected by Enzyme-linked immunosorbent assay (ELISA). The expression of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2 were investigated by quantitative real-time PCR and western blot. In addition, western blotting and immunofluorescence staining were performed to investigate the protein level of inhibitor of nuclear factor-κB (IκB-α) and the translocation of nuclear factor kappa B (NF-κB). For the in vivo study, morin was administered by intra-articular injection in rats, and the gene expression of iNOS and COX-2 was assessed. We showed that morin inhibited the production of NO and PGE(2) as well as the expression of iNOS and COX-2 in interleukin-1-beta (IL-1β)-induced chondrocytes. In addition, morin suppressed the degradation of IκB-α as well as the translocation of NF-κB. In vivo study, morin exerted anti-inflammatory properties in an IL-1β-induced rat OA model. Our data suggest that morin possess potential value in the treatment of OA.

Astaxanthin reduces matrix metalloproteinase expression in human chondrocytes.

Astaxanthin is a red carotenoid pigment which exerts multiple biological activities. However, little is known about the effects of astaxanthin on matrix metalloproteinases (MMPs) in OA. The present study investigated the effects of astaxanthin on MMPs in human chondrocytes. Human chondrocytes were pretreated with astaxanthin at 1, 10 or 50μM, then, cells were stimulated with IL-1β (10ng/ml) for 24h. MMP-1, MMP-3 and MMP-13 were observed. We found that astaxanthin reduced the expression of MMP-1, MMP-3 and MMP-13 as well as the phosphorylation of two mitogen-activated protein kinases (MAPK) (p38 and ERK1/2) in IL-1β-stimulated chondrocytes. Astaxanthin also blocked the IκB-α degradation. These results suggest that astaxanthin may be beneficial in the treatment of OA.

Baicalein Inhibits MMPs Expression via a MAPK-Dependent Mechanism in Chondrocytes

Background: Baicalein is a flavonoid isolated from Scutellaria baicalensis Georgi. Here, we investigated the anti-osteoarthritic effect of baicalein in vitro and in vivo. Methods: Interleukin-1 beta (IL-1β)-induced chondrocytes were treated with different concentrations of baicalein, real-time PCR and ELISA were performed to detect the matrix metalloproteinases (MMPs) expression. Western blot was used to evaluate the mitogen-activated protein kinase (MAPK) expression. In experimental osteoarthritis (OA), rabbits were treated with baicalein, gross morphological and histological assessment was performed to evaluate the cartilage damage. Results: Baicalein significantly reduced the expression of MMPs in vitro and in vivo. Moreover, baicalein significantly reduced the phosphorylation of p38 and extracellular signal regulated kinase (ERK), but not of c-Jun N-terminal kinase (JNK). In addition, intra-articular injection of baicalein ameliorated the cartilage damage in a rabbit model of OA induced by anterior cruciate ligament transection (ACLT). Conclusions: The results indicate that baicalein may be considered as a potential agent for OA treatment.

Sphingosine-1-phosphate: a potential therapeutic target for rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease, which has as its primary target, the synovial tissues and articular cartilage. The current pharmacological treatment of RA includes non-steroidal anti-inflammatory drugs, corticosteroids, and disease-modifying anti-rheumatic drugs. Newer biological agents that work by inactivation of proinflammatory cytokines are available for treatment of RA. Sphingosine-1-phosphate (S1P) is a bioactive lipid that is generated from phosphorylation of sphingosine by activation of sphingosine kinase, and has been implicated as an important mediator in pathophysiological processes, including cell growth, differentiation, migration and survival, and angiogenesis. Several studies have explored the role of S1P in the pathogenesis of RA. The aim of this article was to review the biology and distribution of S1P, together with its role in RA, and to discuss its potential as a therapeutic target for RA.

Morin exerts antiosteoarthritic properties: an in vitro and in vivo study.

Morin is a flavonoid isolated from members of the Moraceae family. Morin has been reported to possess antioxidative and anticarcinogenic activities. However, the antiosteoarthritic properties of morin have not been investigated. In this study, we evaluate the antiarthritic properties of morin through in vitro and in vivo studies. We examined the effects of morin on the expression levels of matrix metalloproteinase (MMP)-3, MMP-13 and tissue inhibitors of metalloproteinase (TIMP)-1 in interleukin-1β (IL-1β)-induced rat chondrocytes by realtime polymerase chain reaction and Western blotting. The effects of morin on the phosphorylation of mitogen-activated protein kinases were also investigated. The in vivo antiosteoarthritic effects of morin were evaluated in the rat model of anterior cruciate ligament transection (ACLT)-induced osteoarthritis (OA). We found that morin inhibited the expression of MMP-3 and MMP-13 and increased the expression of TIMP-1 in IL-1β-induced rat chondrocytes. In addition, morin inhibited IL-1β-induced phosphorylation of extracellular signal-regulated kinase and p38. For the in vivo study in a rat model of OA induced by ACLT, in which morin was orally administered to rat, the results show that morin suppressed cartilage degradation. Our results suggest that morin may be considered as a possible therapeutic agent for the treatment of OA.

Acacetin inhibits expression of matrix metalloproteinases via a MAPK-dependent mechanism in fibroblast-like synoviocytes

It is well known that rheumatoid arthritis (RA) is an autoimmune joint disease in which fibroblast‐like synoviocytes (FLSs) play a pivotal role. In this study, we investigated the anti‐arthritic properties of acacetin in FLSs. The expression of matrix metalloproteinase (MMP)‐1, MMP‐3 and MMP‐13 were investigated by quantitative RT‐PCR and western blot at gene and protein levels. At the same time, the phosphorylation of mitogen‐activated protein kinases (MAPK) was investigated. The DNA‐binding activity of NF‐κB was investigated by electrophoretic mobility shift assay. We found that acacetin inhibits p38 and JNK phosphorylation and reduces MMP‐1, MMP‐3 and MMP‐13 expression in interleukin‐1β‐induced FLSs. Our results suggest that acacetin has antiarthritic effects in FLSs. Thus, acacetin should be further studied for the treatment of arthritis.