Cytokines as biochemical markers for knee osteoarthritis

Osteoarthritis(OA) is a debilitating degenerative joint disease particularly affecting weightbearing joints within the body, principally the hips and knees. Current radiographic techniques are insufficient to show biochemical changes within joint tissue which can occur many years before symptoms become apparent. The need for better diagnostic and prognostic tools is heightened with the prevalence of OA set to increase in aging and obese populations. As inflammation is increasingly beingconsidered an important part of OAs pathophysiology, cytokines are being assessed as possible candidates for biochemical markers. Cytokines, both pro- and antiinflammatory, as well as angiogenic and chemotactic, have in recent years been studied for relevant characteristics. Biochemical markers show promise in determination of the severity of disease in addition to monitoring of the efficacy and safety of disease-modifying OA drugs, with the potential to act as diagnostic and prognostic tools. Currently, the diagnostic power of interleukin(IL)-6 and the relationship to disease burden of IL-1β, IL-15, tumor necrosis factor-α, and vascular endothelial growth factor make these the best candidates for assessment. Grouping appropriate cytokine markers together and assessing them collectively alongside other bone and cartilage degradation products will yield a more statistically powerful tool in research and clinical applications, and additionally aid in distinguishing between OA and a number of other diseases in which cytokines are known to have an involvement. Further large scale studies are needed to assess the validity and efficacy of current biomarkers, and to discover other potential biomarker candidates.

Increased osteopontin and liver stiffness measurement by transient elastography in biliary atresia

AIM: To analyze plasma osteopontin levels and liver stiffness using transient elastography in postoperative biliary atresia (BA) children compared with healthy controls. METHODS: Thirty children with postoperative BA and 10 normal controls were enrolled. The patients were categorized into two groups according to their jaundicestatus. Plasma levels of osteopontin were determined using commercially available enzyme-linked immunosorbent assay. Liver stiffness was measured by using transient elastography (Fibroscan). Ten validated Fibroscan measurements were performed in each patient and control with the result expressed in kilopascals (kPa). RESULTS: Plasma osteopontin was significantly elevated in BA children compared with that of healthy controls (47.0 ± 56.4 ng/mL vs 15.1 ± 15.0 ng/mL, P = 0.01). The liver stiffness measurement was markedly elevated in the patients with BA compared with that of controls (26.9 ± 24.6 kPa vs 3.9 ± 0.7 kPa, P = 0.001). Subgroup analysis showed that the BA patients with jaundice had more pronounced plasma osteopontin levels than those without jaundice (87.1 ± 61.6 ng/mL vs 11.9 ± 6.1 ng/mL, P = 0.001). Furthermore, the mean liver stiffness was significantly greater in the jaundiced BA patients compared with non-jaundiced patients (47.7 ± 21.8 kPa vs 8.7 ± 3.0 kPa, P = 0.001). Additionally, plasma osteopontin was positively related to serum total bilirubin (r = 0.64, P < 0.001). There was also a correlation between plasma osteopontin and liver stiffness values (r = 0.60, P < 0.001). CONCLUSION: High plasma osteopontin positively correlated with degree of hepatic fibrosis and could be used as a biochemical parameter reflecting disease severity in postoperative BA children.

Adipokines: Biomarkers for osteoarthritis?

Osteoarthritis(OA)is one of the most common degenerative joint diseases in aging population.Obesity is an important risk factor for initiation and progression of OA.It is accepted that excess body weight may lead to cartilage degeneration by increasing the mechanical forces across weight-bearing joints.However,emerging data suggest that additional metabolic factors released mainly by white adipose tissue may also be responsible for the high prevalence of OA among obese people.Adipocyte-derived molecules‘‘adipokines’’have prompt much interest in OA pathophysiological research over the past decade since they play an important role in cartilage and bone homeostasis.Therefore,the aim of this review is to summarize the current knowledge on the role of adipokines including leptin,adiponectin,visfatin and resistin in OA and their potential to be used as biomarkers for earlier diagnosis,classifying disease severity,monitoring disease progression,and testing pharmacological interventions for OA.In OA patients,leptin,visfatin and resistin showed increased production whereas adiponectin showed decreased production.Leptin and adiponectin are far more studied than visfatin and resistin.Importantly,altered adipokine levels also contribute to a wide range of diseases.Further experiments are still crucial for understanding the relationship between adipokines and OA.

Mesenchymal stem cells for cartilage regeneration in osteoarthritis

Osteoarthritis(OA) is a slowly progressive disease where cartilage of the synovial joint degenerates. It is most common in the elderly where patients experience pain and reduce physical activity. In combination with lack of conventional treatment, patients are often left with no other choices than arthroplasty. Over the last years, multipotent stromal cells have been used in efforts to treat OA. Mesenchymal stem/progenitor cells(MSCs) are stromal cells that can differentiate into bone, fat, and cartilage cells. They reside within bone marrow and fat. MSCs can also be found in synovial joints where they affect the progression of OA. They can be isolated and proliferated in an incubator before being applied in clinical trials. When it comes to treatment, emphasis has hitherto been on autologous MSCs, but allogenic cells from healthy donors are emerging as another source of the cells. The first adaptations of MSCs revolved in the use of cellrich matrix, delivered as invasive surgical procedure, which resulted in production of hyaline cartilage and fibrocartilage. However, the demand for less invasive delivery of cells has prompted the use of direct intraarticular injections, wherein a large amount of suspended cells are implanted in the cartilage defect.

Adiponectin as a novel biomarker for liver fibrosis

Adiponectin is known to play primary roles in the regulation of systemic glucose homeostasis and lipid metabolism. Interestingly, emerging evidence indicates beneficial effects of adiponectin on liver fibrosis; however, the exact mechanisms of this action remain unclear. Herein, we aimed to summarize the recent findings regarding the role of adiponectin in liver fibrogenesis and update the current comprehensive knowledge regarding usefulness of adiponectin-based treatments in liver fibrosis. Adiponectin has been demonstrated to have an anti-fibrotic action in the liver by blocking the activation of hepatic stellate cellmediated adenosine monophosphate-activated protein kinase and peroxisome proliferator-activated receptoralpha pathways, which in turn diminish the expression of pro-fibrotic genes. In addition, hyperadiponectinemia was noted in patients with various chronic liver diseases(CLDs)-related liver fibrosis. An increase in circulating adiponectin levels was also found to be associated with the development of liver fibrosis, indicating a role of adiponectin as a non-invasive biomarker for predicting the progression of liver fibrosis. It is therefore reasonable to speculate that adiponectin may be developed as a new therapeutic candidate for the treatment of liver fibrosis. Nonetheless, future observations are still necessary to fully elucidate the extent of the effects of adiponectin onliver fibrotic outcomes, in order to modify adiponectin as an anti-fibrotic therapy that would speed up fibrosis reversal in patients with CLD.

Association of adiponectin gene polymorphisms with knee osteoarthritis

AIM To investigate the possible relationship of adiponectin(ADIPOQ) gene polymorphisms, plasma adiponectin, and the risk of knee osteoarthritis(OA).METHODS A total of 398 subjects, 202 knee OA patients and 196 healthy individuals, were enrolled in the case-control study. Genotyping at +45T/G(rs2241766) and +276G/T(rs1501299) loci was performed using polymerase chain reaction-restriction fragment length polymorphism. Plasma adiponectin levels were assessed using enzymelinked immunosorbent assay. OA severity was determined using the Kellgren-Lawrence(KL) grading system.RESULTS No significant associations were observed in the genotype distributions and allele frequencies at two loci of +45T/G and +276G/T polymorphisms in the ADIPOQ betweenknee OA patients and control subjects. There was a significant association between genotype distribution of +276G/T polymorphism and KL grade 2, 3 or 4(P = 0.037, P = 0.046, P = 0.016, respectively). At +45T/G locus, the percentage of GG genotype was notably greater in control subjects(13.40%) compared with OA subjects(1.70%)(P = 0.023). Plasma adiponectin was markedly decreased in OA subjects compared with control subjects(P = 0.03). Likewise, circulating adiponectin in OA subjects was notably lesser than that in control subjects in GG genotype of +45T/G(P = 0.029) and +276G/T polymorphisms(P = 0.012).CONCLUSION Polymorphisms +45T/G and +276G/T of the ADIPOQ gene might not be responsible for OA susceptibility among Thais.

Elevation of serum urokinase plasminogen activator receptor and liver stiffness in postoperative biliary atresia

AIM To investigate serum urokinase-type plasminogen activator receptor(u PAR) and liver stiffness in biliary atresia(BA) and examine the correlation of circulating u PAR, liver stiffness, and clinical outcomes in postoperative BA children.METHODS Eighty-five post Kasai BA children and 24 control subjects were registered. Circulating u PAR was measured using enzyme-linked immunosorbent essay. Liver stiffness was analyzed using transient elastography.RESULTS BA children had significantly greater circulating u PAR andliver stiffness scores than control subjects(P < 0.001). Circulating u PAR and liver stiffness were substantially higher in jaundiced BA children than non-jaundiced BA children(P < 0.001). In addition, circulating u PAR was positively associated with serum aspartate aminotransferase(r = 0.507, P < 0.001), alanine aminotransferase(r = 0.364, P < 0.001), total bilirubin(r = 0.559, P < 0.001), alkaline phosphatase(r = 0.325, P < 0.001), and liver stiffness scores(r = 0.508, P < 0.001).CONCLUSION Circulating u PAR and liver stiffness values were greater in BA children than healthy controls. The increased circulating u PAR was associated with liver dysfunction in BA. As a consequence, serum u PAR and liver stiffness may be used as noninvasive biomarkers indicating the progression of liver fibrosis in post Kasai BA.

Glomus tumors of the fingers:Expression of vascular endothelial growth factor

Glomus tumors are uncommon,benign,small neuro-vascular neoplasms derived from glomus bodies in the reticular dermis. Glomus bodies are found throughout the body to regulate body temperature and skin circulation; however,they are concentrated in the fingers and the sole of the foot. The typical presentation is a solitary nodule in the subungual or periungual area of the distal phalanx. The primary treatment of choice is surgical removal. We investigated expression of vascular endothelial growth factor(VEGF) using immunohistochemistry in glomus tumors of the fingers. All five glomus tumor samples were positive for VEGF expression. VEGF immunoreactivity was largely localized to the cytoplasm of tumor cells,suggesting a contribution of VEGF to the vascularization of glomus tumors.

Low bone mineral density and the severity of cholestasis in biliary atresia

AIM To investigate the prevalence of osteopenia and osteoporosis in postoperative biliary atresia(BA) children and the association of bone mineral density(BMD) and biochemical parameters in post Kasai BA subjects. METHODS A total of 70 patients with post Kasai BA were enrolled in this prospective study. The patients were classified into two groups according to their jaundice status. BMD of the lumbar spine was analyzed using dual energyX-ray absorptiometry.RESULTS The prevalence of low bone mass(osteopenia and osteoporosis) in BA patients were 51.4%(36 out of 70). Ten patients(35.7%) in the jaundice group and 8 patients(19.0%) in the non-jaundice group had osteopenia. Sixteen patients(57.1%) in the jaundice group and 2 patients(4.8%) in the no jaundice group had osteoporosis. In addition, lumbar spine BMD Z-score was substantially lower in the jaundice BA patients compared with non-jaundice patients. BA subjects with persistent jaundice had significantly lower serum 25-hydroxyvitamin D than those without jaundice. Further analysis revealed that lumbar spine BMD was correlated with age(r = 0.774, P < 0.001), serum albumin(r = 0.333, P = 0.005), total bilirubin(r =-0.476, P < 0.001), aspartate aminotransferase(r =-0.583, P < 0.001), alanine aminotransferase(r =-0.428, P < 0.001), and alkaline phosphatase(r =-0.456, P < 0.001).CONCLUSION Low BMD was associated with biochemical parameters reflecting the severity of cholestasis in post Kasai BA patients.

Vitamin D and spine surgery

Vitamin D is crucial for musculoskeletal health, maintenance, and function. Vitamin D insufficiency is common among patients undergoing spine surgery and the ideal vitamin D level for spine surgery has yet to be investigated. There is a high prevalence of hypovitaminosis D in patients with musculoskeletal pain regardless of surgical intervention. With the frequency and costs of spine surgery increasing, it is imperative that efforts are continued to reduce the impact on patients and healthcare services. Studies into vitamin D and its associations with orthopaedic surgery have yielded alarming findings with regards to the prevalence of vitamin D deficiency. Importantly, altered vitamin D status also contributes to a wide range of disease conditions. Therefore, future investigations are still essential for better understanding the relationship between vitamin D and spine surgery outcomes. Whilst further research is required to fully elucidate the extent of the effects of hypovitaminosis D has on surgical outcomes, it is strongly advisable to reduce the impacts by appropriate vitamin D supplementation of deficient and at-risk patients.

膝骨关节炎患者全血白细胞线粒体DNA复制数量和血浆炎性细胞因子的相关性研究（英文）

目的:本实验研究全血白细胞线粒体DNA复制数量(mtDNACN)和血浆炎性细胞因子在膝骨关节炎患者中的变化和其相关性。创新点:探讨了老年(50~80岁)膝骨关节炎患者白细胞mtDNACN和血浆炎性细胞因子水平及二者的关系。方法:分别收集膝骨关节炎组和对照组血液样本并对膝关节评分(Kellgren-Lawren grading)。使用实时定量聚合酶链反应(qRT-PCR)检测相对mtDNACN;使用多重免疫分析(multiplex immunoassay)测定血浆中10种炎性细胞因子水平;应用线性相关、Logistic回归和主成分分析(PCA)揭示骨关节炎白细胞mtDNACN和血浆炎性细胞因子的相关性。结论:血浆中白介素4(IL-4)、IL-6和全血白细胞mtDNACN可能是膝骨关节炎有效的生物标志物;IL-5则对mtDNACN减少具有潜在的影响。