Role of infrapatellar fat pad in pathological process of knee osteoarthritis: Future applications in treatment.

It has been found that obese people have a higher proportion in suffering from osteoarthritis (OA), not only in the weight-bearing joints like knee and hip joints, even in non-weight-bearing joints such as hand joints. One of the reasons is because the large amount of adipose tissue secretes some factors, which can promote the occurrence of arthritis. As an important structure of the knee joint, the infrapatellar fat pad (IPFP) is actually a piece of adipose tissue. The aim of this review is to offer a comprehensive view of the anatomy and physiological characteristics of IPFP and its relationship with the pathological process of OA, indicating the important function of IPFP in OA. At the same time, with the development of adipose derived stem cells in the treatment of OA, owing to its special advantages, the IPFP is becoming a kind of important, minimally invasive fat stem cell source, providing a new approach for the treatment of OA. We hope that this review will offer an overview of all published data regarding the IPFP and will indicate novel directions for future research.

Efficacy and Safety of Tranexamic Acid in Intertrochanteric Fractures: A Single-Blind Randomized Controlled Trial.

OBJECTIVE: To investigate the efficacy and safety of tranexamic acid (TXA) in the reduction of bleeding and the need for transfusion in elderly intertrochanteric fracture patients. METHODS: A total of 100 patients with intertrochanteric fractures undergoing surgery were enrolled and randomly allocated to the TXA group in which patients (75.10 ± 8.27 years old) were treated with 1 g of TXA, or the control group (77.82 ± 6.42 years old) treated with a placebo. Surgery was performed by two senior orthopaedic surgeons from two institutions. The proximal femoral nail antirotation (PFNA) was conducted using the standard procedure. Three outcome measures, including blood loss, transfusion, and complications, were recorded. Blood loss and transfusion were investigated to assess TXA's effectiveness, while complications were investigated to assess TXA's safety. Statistical indicators for blood loss included total, intraoperative, postoperative, and hidden blood loss volumes, calculated by hemoglobin levels, hematocrit levels, and drainage volume. The number and amount of blood transfusions were recorded. Complications associated with surgery, including deep vein thrombosis, pulmonary embolism, wound hematoma, wound infection, cardiovascular and cerebrovascular accidents, and respiratory infections, were also recorded. RESULTS: All patients were followed up for 1 month after surgery. There were no significant differences in demographic and clinical characteristics between the two groups. The TXA group suffered significantly less total blood loss (563.37 ± 197.51 vs 819.25 ± 273.96 mL, 95% CI: -349.49 to -162.27, P < 0.01), intraoperative blood loss (140.3 ± 80.64 vs 230.5 ± 130.56 mL, 95% CI -132.74 to -47.66, P < 0.01), and hidden blood loss (410.42 ± 178.23 vs 571.19 ± 218.13 mL, 95% CI: -238.85 to -82.69, P < 0.01) than the control group. However, postoperative total blood loss was not significantly different (97.5 ± 20.93 vs 94.7 ± 35.78 mL; P = 0.63). A total of 5 patients from the TXA group and 27 from the control group received packed RBC for postoperative transfusion, but the mean number of transfusion units was not significantly different between groups. Complications including deep vein thrombosis, pulmonary embolism, myocardial infarction, ischemic cerebral infarction, hematoma, and infection were observed in both groups, but no significant differences were found. CONCLUSIONS: In intertrochanteric fracture surgery performed using PFNA, intravenous administration of TXA significantly reduced the risk of intraoperative, total and hidden blood loss, in addition to the need for allogeneic transfusion, without increasing the rate of complications.

Paeoniflorin inhibits IL-1ß-induced MMP secretion via the NF-κB pathway in chondrocytes.

Paeoniflorin serves important cellular roles, exerting anti-cancer, anti-inflammatory and anti-pulmonary fibrosis effects and possesses immune-modulatory properties. However, the exact role of paeoniflorin in the pathogenesis of osteoarthritis (OA) remains unclear. The aim of the present study was to investigate the effects of paeoniflorin on articular surfaces in vitro. Rat chondrocytes were cultured in vitro and an MTT assay was performed to assess chondrocyte survival. Following treatment with interleukin (IL)-1ß and paeoniflorin, the production of matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases-1 (TIMP-1) was examined using reverse transcription-quantitative polymerase chain reaction and western blotting. The interleukin (IL)-1ß-induced nuclear factor (NF)-κB pathway activation was also investigated. The results demonstrated that paeoniflorin was able to downregulate the expression of MMP and increase the expression of TIMP-1ntmRNA and protein in IL-1ß-induced rat chondrocytes. Furthermore, treating chondrocytes with paeoniflorin blocked the activation of NF-κB. These results suggest that paeoniflorin may serve am anti-catabolic role in the progression of OA and may be an effective preventative treatment for OA.

Inhibitory Effects of Danshen components on CYP2C8 and CYP2J2.

The use of Chinese herbal medicines and natural products has become increasingly popular in both China and Western societies as an alternative medicine for the treatment of diseases or as a health supplement. Danshen, the dried root of Salvia miltiorrhiza (Fam.Labiatae), which is rich in phenolic acids and tanshinones, is a widely used herbal medicine for the treatment of cardio-cerebrovascular diseases. The goal of this study was to examine the inhibitory effects of fifteen components derived from Danshen on CYP2C8 and CYP2J2, which are expressed both in human liver and cardiovascular systems. Recombinant CYP2C8 and CYP2J2 were used, and the mechanism, kinetics, and type of inhibition were determined. Taxol 6-hydroxylation and astemizole O-desmethyastemizole were determined as probe activities for CYP2C8 and CYP2J2, respectively. Metabolites formations were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The results demonstrated that salvianolic acid A was a competitive inhibitor of CYP2C8 (Ki = 2.5 µM) and mixed-type inhibitor of CYP2J2 (Ki = 7.44 µM). Salvianolic acid C had moderate noncompetitive and mixed-type inhibitions on CYP2C8 (Ki = 4.82 µM) and CYP2J2 (Ki = 5.75 µM), respectively. Tanshinone IIA was a moderate competitive inhibitor of CYP2C8 (Ki = 1.18 µM). Dihydrotanshinone I had moderate noncompetitive inhibition on CYP2J2 (Ki = 6.59 µM), but mechanism-based inhibition on CYP2C8 (KI = 0.43 µM, kinact = 0.097 min-1). Tanshinone I was a moderate competitive inhibitor of CYP2C8 (Ki = 4.20 µM). These findings suggested that Danshen preparations appear not likely to pose a significant risk of drug interactions mediated by CYP2C8 after oral administration; but their inhibitory effects on intestinal CYP2J2 mediated drug metabolism should not be neglected when they are given orally in combination with other drugs. Additionally, this study provided novel insights into the underling pharmacological mechanisms of Danshen components from the perspective of CYP2C8 and CYP2J2 inhibition.

Computed tomography angiography and magnetic resonance imaging performance of acute segmental single compartment syndrome following an Achilles tendon repair: A case report and literature review.

Acute compartment syndrome of the lower extremity is a serious postinjury complication that requires emergency treatment. Early diagnosis is of paramount importance for a good outcome. Four muscle compartments in the calf (anterior, lateral, deep posterior, and superficial posterior) may be individually or collectively affected. Acute segmental single-compartment syndrome is an extremely rare condition characterized by high pressure in a single compartment space with threatening of the segmental tissue viability. In this case report, we describe a young man with Achilles tendon rupture who complained of postoperative pain in the anterior tibial region. Emergent computed tomography angiography and magnetic resonance imaging revealed local muscle edema. Segmental anterior compartment syndrome was diagnosed and fasciotomy was performed.

A strategy for screening active lead compounds and functional compound combinations from herbal medicines based on pharmacophore filtering and knockout/knockin chromatography.

Screening and deciphering active natural products of herbal medicines are of great importance for modern drug discovery. In this study, a novel strategy was proposed to rapidly filter ineffective compounds and target the most potential leads. The aim is to answer the key question of what components are responsible for the holistic bioactivity of an herbal product. To support the strategy, the pharmacophore-guided knockout/knockin chromatography was established for the first time. The greatest advantage of this method is that any interesting components could be automatically fished or knocked out. The method validation shows that the herbal extract was accurately reconstructed according to the experimental design. By combining with bioactivity assays, we demonstrated that "functional compound combination (FCC)", which is the core and indispensable effective part, could be discovered from an herbal medicine and suitable as marker compounds for quality control. The applicable objects of the strategy include single herbs, herbal formulas and commercially herbal preparations. As an illustrative case study, the strategy was successfully applied to simultaneously determine active leads and the FCC in Dan-Qi formula which shows excellent free radical scavenging activity. The potential mechanisms of compounds in Dan-Qi formula reacting with three different free radicals were systematically reported for the first time. This strategy was expected to unveil the mystery of herbal medicines and inspire a natural product-based drug discovery.

Expression of vaspin in the joint and the levels in the serum and synovial fluid of patients with osteoarthritis.

The aim of this study was to determine the expression of vaspin in the joint and investigate the distribution between paired serum and synovial fluid (SF) in osteoarthritis (OA) patients, and serum in healthy controls. The gene expression of vaspin was measured by quantitative real-time polymerase chain reaction (qPCR) in the OA joint tissues. The vaspin protein expression in the cartilage, synovium and osteophyte from OA patients who required total knee replacement (TKR) were detected by immunohistochemistry (IHC). Levels of vaspin in serum and SF were analyzed by enzyme-linked immunosorbent assay (ELISA), including 26 OA patients and 23 healthy controls. All the joint tissues including cartilage, synovium, meniscus, infrapatellar fat pad and osteophyte from OA patients expressed vaspin messenger RNA (mRNA), and the expression of vaspin protein was observed in OA cartilage, synovium and osteophyte. Furthermore, serum vaspin was reduced in OA patients compared to healthy controls, and serum vaspin levels from OA patients exceed those in the paired SF. Serum or SF vaspin were not related to age, gender, or body mass index (BMI). These results suggest that vaspin may be involved in the pathophysiology of OA and may have local effects in the joint during the process of OA.

Hinokitiol reduces matrix metalloproteinase expression by inhibiting Wnt/ß-Catenin signaling in vitro and in vivo.

OBJECTIVE: In this study, we investigated the effects of hinokitiol on matrix metalloproteinase (MMP)-1, -3, -13, collagen type II (Col2a1) and ß-catenin expressions in rat chondrocytes induced by interleukin-1ß and in an experimental rat model induced by intra-articular injection of mono-iodoacetate (MIA) into the knee. METHODS: Chondrocytes were cultured from the articular cartilage of 2-week-old rats. Passaged chondrocytes were pretreated with hinokitiol for 2h followed by co-incubation with IL-1ß for 24h. Quantitative real-time polymerase chain reaction and Western blotting were used to assess the expression of MMP-1, -3, -13, Col2a1 and ß-catenin. Chondrocytes were also treated with Licl, Dickkopf-1, and/or hinokitiol for 24h, the MMP-1, -3, -13 and ß-catenin protein levels determined by Western blotting. The in vivo effects of hinokitiol were assessed by morphological and histological analyses following MIA injection. RESULTS: Hinokitiol inhibited IL-1ß-stimulated MMP-1,-3 and -13 expressions and IL-1ß-induced activation of intracellular ß-catenin proteins in cultured chondrocytes. In vivo, morphological and histological examinations demonstrated that hinokitiol significantly ameliorated cartilage degeneration. CONCLUSIONS: Hinokitiol is an effective anti-inflammatory reagent that acts by inhibiting the Wnt/ß-catenin signaling pathway and could be a promising therapeutic agent for the prevention and treatment of osteoarthritis.

Visceral adipose tissue-derived serine protease inhibitor inhibits interleukin-1ß-induced catabolic and inflammatory responses in murine chondrocytes.

Visceral adipose tissue-derived serine protease inhibitor (vaspin) is a newly identified member of the adipocytokine family, whose precise role in chondrocyte metabolism remains to be elucidated. The aim of the present study was to investigate the effect of vaspin on chondrocytes. The cell viability and the cytotoxicity of vaspin in chondrocytes were examined. Furthermore, the gene expression of matrix metalloproteinases-2 and -9, a disintegrin and metalloproteinase with thrombospondin motifs 4 and 5 and cathepsin D was also examined, as well as the protein production of cyclooxygenase-2, prostaglandin E2 and inducible nitrous oxide synthase following treatment with different concentrations of vaspin in the absence or presence of interleukin-1-beta (IL-1ß). In addition, the protein levels of the inhibitor of nuclear factor-κB (IκB-α) and the phosphorylation of nuclear factor kappa B (NF­κB) were investigated. Vaspin was not able to stimulate the proliferation of chondrocytes and demonstrated no significant cytotoxic effect at concentrations of 10-500 ng/ml following coincubation for 24 and 48 h. However, vaspin inhibited IL-1ß­induced production of catabolic factors and inflammatory mediators in chondrocytes, and also suppressed the phosphorylation of NF­κB and the degradation of IκB­α. The data from the present study suggested that vaspin has a protective effect in chondrocyte metabolism and is an important factor in the pathophysiology of osteoarthritis.

Do we really need closed-suction drainage in total hip arthroplasty? A meta-analysis.

PURPOSE: The clinical use of closed-suction drainage, which aims to reduce postoperative wound haematomas and infection, is common. This study was performed to determine whether closed-suction drainage is safe and effective in promoting wound healing and reducing blood loss and other complications compared with no-drainage in total hip arthroplasty. METHODS: The literature search was based on PubMed, the Cochrane Library, MEDLINE, and EMBASE. The data were evaluated using the generic evaluation tool designed by the Cochrane Bone, Joint and Muscle Trauma Group, and then analysed using RevMan 5.0. Twenty randomised controlled trials involving 3,186 patients were included in our analysis. RESULTS: The results of our meta-analysis indicate that closed-suction drainage reduces the requirement for dressing reinforcement, but increases the rate of homologous blood transfusion. No significant difference was observed in the incidence of infection, blood loss, changes in haemoglobin and haematocrit, functional assessment, or other complications when the drainage group was compared with the no-drainage group. CONCLUSIONS: Our results of the comparison between closed-suction drainage and no drainage in THA have indicated that the routine use of closed-suction drainage for elective total hip arthroplasty may be of more harm than benefit.

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.