Jia-Peng Bao

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.

Lubricin: a novel potential biotherapeutic approaches for the treatment of osteoarthritis

Osteoarthritis (OA) is a multi-factor disorder of sinovial joints, which characterized by escalated degeneration and loss of articular cartilage. Treatment of OA is a critical unmet need in medicine for regeneration of damaged articular cartilage in elderly. On the other hand, lubricin, a glycoprotein specifically synthesized by chondrocytes located at the surface of articular cartilage, has been shown to provide boundary lubrication of congruent articular surfaces under conditions of high contact pressure and near zero sliding speed. Lubrication of these surfaces is critical to normal joint function, while different gene expressions of lubricin had been found in the synovium of rheumatoid arthritis (RA) and OA. Moreover, mutations or lacking of lubricin gene have been shown to link to the joint disease such as camptodactyly-arthropathy-coxa vara-pericarditis syndrome (CACP), synovial hyperplasia and failure of joint function, suggesting an important role of lubricin in the pathogenesis of these joint disease. Recent studies demonstrate that administration with recombinant lubricin in the joint cavity would be effective in the prevention of cartilage degeneration in animal OA models. Therefore, a treatment with lubricin which would protect cartilage in vivo would be desirable. This article reviews recent findings with regard to the possible role of lubricin in the progression of OA, and further discusses lubricin as a novel potential biotherapeutic approaches for the treatment 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.

Variation patterns of two degradation enzyme systems in articular cartilage in different stages of osteoarthritis: Regulation by dehydroepiandrosterone

BACKGROUND Osteoarthritis (OA) is a multifactorial degenerative joint disease in which the cartilaginous matrix of the articular joint is destroyed in a continuous process. We evaluated mRNA levels of cysteine proteinases/cystatin C system and urokinase plasminogen activator/plasminogen activator inhibitor-1 (uPA/PAI-1) system in articular cartilage and regulation by dehydroepiandrosterone (DHEA) in different stages of osteoarthritis (OA). METHODS One hundred and eight rabbits underwent anterior cruciate ligament transection (ACLT) in the left knee, 54 received weekly intra-articular injections of DHEA (100 micromol/l) 0.3 ml 3 weeks after transaction as DHEA group. Thirty-six rabbits (18 from 2 groups respectively) were euthanized 6, 9, and 12 weeks after ACLT. All left knee joints were assessed by gross morphology and histology, meantime the gene expression from articular cartilage was analyzed. RESULTS Cathepsins and uPA gene increased significantly 6 weeks and reached peak in the 9th week, while declined to extremely low levels 12 weeks after ACLT. Cystatin C decreased accompanied by OA progression, while PAI-1 expressed in the same trend with uPA. Additionally, these 2 enzyme systems were markedly suppressed by DHEA 6 and 9 weeks after ACLT but not in the 12th week. CONCLUSION The variation of these 2 enzyme systems was closely related to the progression of OA, and could be regulated by DHEA especially in the early and medium stages 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.

Visfatin: a potential therapeutic target for rheumatoid arthritis.

Rheumatoid arthritis (RA) is usually a chronic, systemic inflammatory disorder primarily targeting the synovium and articular cartilage. It is incurable, costly and responds poorly to treatment. Methotrexate alone or in combination with conventional and/or biological disease-modifying antirheumatic drugs (DMARDs) is often used to induce remission of active disease. The effectiveness of treatment is, however, limited and most patients develop chronic disability and require total knee arthroplasty or total hip replacement. Emerging therapies targeting specific cytokines and growth factors in the RA inflammatory cascade offer potent new means of modifying disease activity. Recently, increased concentrations of adipokines, including visfatin, mainly produced by adipocytes in serum and joint synovial fluid, were found in RA patients. Visfatin has important pro-inflammatory and catabolic roles in RA pathogenesis and is now being studied as a potential therapeutic target for RA. Here we discuss the relationship between visfatin and RA and its potential as a therapeutic target for RA.

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.

Tetrandrine Inhibits the Wnt/β-Catenin Signalling Pathway and Alleviates Osteoarthritis: An In Vitro and In Vivo Study

There is currently no effective drug treatment for the early phase of osteoarthritis (OA), one of the most common senile diseases. The goal of this study was to investigate the protective effect of the tetrandrine (Tet) on OA, in vitro and in vivo. In an in vitro experiment, quantitative real-time polymerase chain reaction (qRT-PCR) was used to investigate changes in gene expression upon the addition of Tet in chondrocytes processed with IL-1β; changes in protein profiles were assessed by Western blotting. In vivo, to determine whether Tet has the protective effects on articular cartilage, a rabbit anterior cruciate ligament transaction model of OA was established. Expression of matrix metalloproteinase and β-catenin genes increased significantly, while that of tissue inhibitor of metalloproteinase-1 decreased significantly in the OA group both in vivo and in chondrocytes. However, the changes of expression were reversed by Tet, and there was less cartilage degradation in vivo compared with the OA group, as assessed by histological and macroscopic observations. Thus, Tet may play a useful role in the treatment of OA through the Wnt/β-catenin signalling pathway and has potential for the treatment of OA.