Regulation of Osteoclast Differentiation by Cytokine Networks

Cytokines play a pivotal role in maintaining bone homeostasis. Osteoclasts (OCs), the sole bone resorbing cells, are regulated by numerous cytokines. Macrophage colony-stimulating factor and receptor activator of NF-κB ligand play a central role in OC differentiation, which is also termed osteoclastogenesis. Osteoclastogenic cytokines, including tumor necrosis factor-α, IL-1, IL-6, IL-7, IL-8, IL-11, IL-15, IL-17, IL-23, and IL-34, promote OC differentiation, whereas anti-osteoclastogenic cytokines, including interferon (IFN)-α, IFN-β, IFN-γ, IL-3, IL-4, IL-10, IL-12, IL-27, and IL-33, downregulate OC differentiation. Therefore, dynamic regulation of osteoclastogenic and anti-osteoclastogenic cytokines is important in maintaining the balance between bone-resorbing OCs and bone-forming osteoblasts (OBs), which eventually affects bone integrity. This review outlines the osteoclastogenic and anti-osteoclastogenic properties of cytokines with regard to osteoimmunology, and summarizes our current understanding of the roles these cytokines play in osteoclastogenesis.

Generation of an osteoblast-based artificial niche that supports in vitro B lymphopoiesis

B lymphocytes are produced from hematopoietic stem cells (HSCs) through the highly ordered process of B lymphopoiesis, which is regulated by a complex network of cytokines, chemokines and cell adhesion molecules derived from the hematopoietic niche. Primary osteoblasts function as an osteoblastic niche (OBN) that supports in vitro B lymphopoiesis. However, there are significant limitations to the use of primary osteoblasts, including their relative scarcity and the consistency and efficiency of the limited purification and proliferation of these cells. Thus, development of a stable osteoblast cell line that can function as a biomimetic or artificial OBN is necessary. In this study, we developed a stable osteoblastic cell line, designated OBN4, which functions as an osteoblast-based artificial niche that supports in vitro B lymphopoiesis. We demonstrated that the production of a B220⁺ cell population from Lineage⁻ (Lin⁻) Sca-1⁺ c-Kit⁺ hematopoietic stem and progenitor cells (HSPCs) was increased ~1.7-fold by OBN4 cells relative to production by primary osteoblasts and OP9 cells in coculture experiments. Consistently, OBN4 cells exhibited the highest production of B220⁺ IgM⁺ cell populations (6.7±0.6–13.6±0.6%) in an IL-7- and stromal cell-derived factor 1-dependent manner, with higher production than primary osteoblasts (3.7±0.5–6.4±0.6%) and OP9 cells (1.8±0.6–3.9±0.5%). In addition, the production of B220⁺ IgM⁺ IgD⁺ cell populations was significantly enhanced by OBN4 cells (15.4±1.1–18.9±3.2%) relative to production by primary osteoblasts (9.5±0.6–14.6±1.6%) and OP9 cells (9.1±0.5–10.3±1.8%). We conclude that OBN4 cells support in vitro B lymphopoiesis of Lin⁻ Sca-1⁺ c-Kit⁺ HSPCs more efficiently than primary osteoblasts or OP9 stromal cells.

Rutin induces autophagy in cancer cells

Rutin (3,3′,4′,5,7-pentahydroxyflavone-3-rhamnoglucoside) is a bioactive flavonoid from the plant kingdom. Rutin has been studied as potential anticancer agent due to its wide range of pharmacological properties including antioxidative, anti-inflammatory and anticancer. Autophagy is a conserved intracellular catabolic pathway to maintain cell homeostasis by formation of autophagosome. Processing of autophagy involves various molecules including ULK1 protein kinase complex, Beclin-1–Vps34 lipid kinase complex, ATG5, ATG12, and LC3 (light chain 3). Cargo-carried autophagosomes fuse with lysosomes resulting in autophagolysosome to eliminate vesicles and degrade cargo. However, the actions of rutin on autophagy are not clearly understood. In this study, we analyzed the effect of rutin on autophagy and inflammation in cancer cell lines. Interestingly, rutin induced autophagy in leukemia (THP-1), oral (CA9-22), and lung (A549) cell lines. TNF-α, key modulator of inflammation, was upregulated by inhibition of rutin-induced autophagy. Taken together, these data indicated that rutin induced autophagy and consequently suppressed TNF-α production.

Nurses' Emotional Responses and Ethical Attitudes towards Elderly Patients' DNR Decision / 한국호스피스완화의료학회지

PURPOSE: The purpose of this study was to examine nurses' emotional responses and ethical attitudes towards elderly patients' Do-Not-Resuscitate (DNR) decision. METHODS: Data were collected using a questionnaire which was filled out by 153 nurses who worked in nursing homes and general hospitals. Data were analyzed using real numbers, percentages, means, standard deviations and Pearson's correlation coefficients with SPSS 19.0 program. RESULTS: The average score for ethical attitudes towards the DNR decision was 2.68 out of 4. Under the ethical attitudes category, the highest score was found with a statement that said 'Although they will not perform cardiopulmonary resuscitate (CPR), it is right to do their best with other treatments for DNR Patients'. Items regarding emotional responses to the DNR decision, the average score was 2.36 out of 4. Among them, the highest score was achieved on 'I understand and sympathize'. No significant correlation was found between ethical attitudes and emotional responses in relation to patients' DNR decision (r=-0.12, P=0.13). CONCLUSION: Regarding elderly patients' DNR decision, nurses showed somewhat highly ethical attitudes and slightly positive emotional response. A follow-up study is needed to investigate variables that affect our results.

A Comparison of the Effect of Epidural Patient-Controlled Analgesia with Intravenous Patient-Controlled Analgesia on Pain Control after Posterior Lumbar Instrumented Fusion

OBJECTIVE: Retrospective analysis to compare the effect and complication of epidural patient-controlled analgesia (epidural PCA) with intravenous patient-controlled analgesia (IV PCA) for the treatment of the post-operative pain after posterior lumbar instrumented fusion. METHODS: Sixty patients who underwent posterior lumbar instrumented fusion for degenerative lumbar disease at our institution from September 2007 to January 2008 were enrolled in this study. Out of sixty patients, thirty patients received IV PCA group and thirty patients received epidural PCA group. The pain scale was measured by the visual analogue scale (VAS) score. RESULTS: There were no significant difference between IV PCA group and epidural PCA group on the PCA related complications (p=0.7168). Ten patients in IV PCA group and six patients in epidural PCA group showed PCA related complications. Also, there were no significant differences in reduction of VAS score between two groups on postoperative 2 hours (p=0.9618) and 6 hours (p=0.0744). However, postoperative 12 hours, 24 hours and 48 hours showed the significant differences as mean of reduction of VAS score (p=0.0069, 0.0165, 0.0058 respectively). CONCLUSION: The epidural PCA is more effective method to control the post-operative pain than IV PCA after 12 hours of spinal fusion operation. However, during the first twelve hours after operation, there were no differences between IV PCA and epidural PCA.