Interleukin-32 (IL-32), a recently identified pro-inflammatory cytokine, is involved in the pathogenesis and progression of infections, cancer, chronic inflammation, and autoimmune disease. IL-32γ is the most active isoform in cell death and cell activation among nine distinct isoforms of IL-32. IL-32γ potentiates both osteogenic and osteoclastogenic capacities, and is critical in the coupling of bone resorption and bone formation for maintenance of bone homeostasis. IL-32γ is strongly associated with inflammatory bone disorders such as rheumatoid arthritis, ankylosing spondylitis, and osteoporosis. In this review, we summarize current research on the role of IL-32γ in inflammatory bone disorders, highlighting this cytokine as a novel target for prognostic marker and control of these diseases.
Arthritis, Rheumatoid ; Autoimmune Diseases ; Bone Diseases* ; Bone Resorption ; Cell Death ; Homeostasis ; Inflammation ; Osteogenesis ; Osteoporosis ; Protein Isoforms ; Spondylitis, Ankylosing

Gastric carcinoma is considered to be one of the most prevalent cancers worldwide. We have performed differential-display polymerase chain reaction (DD-PCR) in order to compare the gene expression profile of gastric carcinoma and that of a normal stomach, in an attempt to identifiy differentially expressed genes associated with primary human gastric cancers. One of the down-regulated genes in gastric cancers was identified as regenerating islet-derived 3 alpha (REG3A), also known as hepatocarcinoma-intestine-pancreas/ pancreatitis-associated protein (HIP/PAP). REG3A exhibited relatively high expression levels in normal gastric mucosa. However, REG3A was found to be down-regulated in 67% (20 out of 30 samples) of primary human gastric cancers, as determined by RT-PCR. In addition, REG3A mRNA expression was not detected in stomach cancer cell lines, SNU cells. Immunohistochemical analysis further confirmed the down-regulation of REG3A expression in primary human gastric cancers. Treatment with the demethylating agent, 5-aza-2'-deoxycytidine (5-Aza-dC) resulted in the restoration of REG3A mRNA expression in the gastric cancer cell line, indicating that the transcriptional silencing of REG3A in SNU cell lines was caused by DNA methylation. Taken together, these data indicate that REG3A is down-regulated in most primary human gastric cancer cells, and might be useful in the diagnosis of gastric cancer. Further characterization of the differentially expressed gene, REG3A, should lead to a better understanding of the changes occurring at the molecular level during the development and progression of primary human gastric cancer.
Adult ; Aged ; Cell Line ; Cell Transformation, Neoplastic ; Down-Regulation ; Gastrointestinal Neoplasms/*metabolism ; Gene Expression Profiling ; *Gene Expression Regulation, Neoplastic ; *Gene Silencing ; Humans ; Middle Aged ; Polymerase Chain Reaction ; Proteins/*metabolism

Sphingosine-1-phosphate (S1P) is an important lipid mediator that regulates a diverse range of intracellular cell signaling pathways that are relevant to tissue engineering and regenerative medicine. However, the precise function of S1P in dental pulp stem cells (DPSCs) and its osteogenic differentiation remains unclear. We here investigated the function of S1P/S1P receptor (S1PR)-mediated cellular signaling in the osteogenic differentiation of DPSCs and clarified the fundamental signaling pathway. Our results showed that S1P-treated DPSCs exhibited a low rate of differentiation toward the osteogenic phenotype in association with a marked reduction in osteogenesis-related gene expression and AKT activation. Of note, both S1PR1/S1PR3 and S1PR2 agonists significantly downregulated the expression of osteogenic genes and suppressed AKT activation, resulting in an attenuated osteogenic capacity of DPSCs. Most importantly, an AKT activator completely abrogated the S1P-mediated downregulation of osteoblastic markers and partially prevented S1P-mediated attenuation effects during osteogenesis. Intriguingly, the pro-inflammatory TNF-α cytokine promoted the infiltration of macrophages toward DPSCs and induced S1P production in both DPSCs and macrophages. Our findings indicate that the elevation of S1P under inflammatory conditions suppresses the osteogenic capacity of the DPSCs responsible for regenerative endodontics.
Cell Differentiation ; Cell Proliferation ; Cells, Cultured ; Dental Pulp/metabolism* ; Lysophospholipids ; Osteogenesis ; Proto-Oncogene Proteins c-akt/metabolism* ; Signal Transduction ; Sphingosine/analogs & derivatives* ; Stem Cells