Mesenchymal stem cells (MSCs) can differentiate into multiple cell lineages, including osteoblasts and adipocytes. We reported previously that glucocorticoid-induced leucine zipper (GILZ) inhibits peroxisome proliferator-activated receptor ␥-2 (Ppar␥2) expression and blocks adipocyte differentiation. Here we show that overexpression of GILZ in mouse MSCs, but not MC3T3-E1 osteoblasts, increases alkaline phosphatase activity and enhances mineralized bone nodule formation, whereas knockdown of Gilz reduces MSC osteogenic differentiation capacity. Consistent with these observations, real-time reverse transcription-PCR analysis showed that both basal and differentiation-induced transcripts of the lineage commitment gene Runx2/Cbfa1, as well as osteoblast differentiation marker genes including alkaline phosphatase, type I collagen, and osteocalcin, were all increased in GILZ-expressing cells. In contrast, the mRNA levels of adipogenic Ppar␥2 and C/ebp␣ were significantly reduced in GILZ-expressing cells under both osteogenic and adipogenic conditions. Together, our results demonstrate that GILZ functions as a modulator of MSCs and that overexpression of GILZ shifts the balance between osteogenic and adipogenic differentiation of MSCs toward the osteogenic pathway. These data suggest that GILZ may have therapeutic value for stem cell-based therapies of metabolic bone diseases, such as fracture repair.Bone marrow-derived mesenchymal stem cells (MSCs) 3 are pluripotent and can give rise to several distinct cell lineages, such as osteoblasts, adipocytes, chondrocytes, myocytes, and even neurons under appropriate conditions (1-4). Increasing evidence has shown that adipocytes and osteoblasts are two major pathways and that the relationship between these two is reciprocal, i.e. when the adipogenic pathway is blocked, the MSCs enter the osteogenic pathway, and vice versa (5-9). Thus, balanced MSC osteoblast and adipocyte differentiation is critical for the maintenance of healthy bone and lean body composition, and understanding of the mechanisms by which this balance is modulated will have significant medical implications in stem cell-based therapies. We reported previously that a glucocorticoid (GC)-inducible protein, called GC-induced leucine zipper (GILZ) (10), can inhibit the transcription of a key adipogenic regulator, peroxisome proliferator-activated receptor ␥-2 (Ppar␥2), and blocks adipocyte differentiation of 3T3-L1 cells (11). Gilz is a new member of the leucine zipper protein family and belongs to the transforming growth factor ␤-stimulated clone-22 (Tsc-22) family of transcription factors (12, 13). Members of this family contain three distinct domains: an N terminus TSC box, a middle leucine zipper domain, and a C terminus proline-rich domain. GILZ has been shown to interact with and inhibit the activities of the key inflammatory signaling mediators 15). GILZ can also interact with the mitogen-activated protein kinase family member, Raf1, resulting in inhibition of Raf-1 phosphorylation and, subsequently, inh...

BackgroundAustronesian is a linguistic family spread in most areas of the Southeast Asia, the Pacific Ocean, and the Indian Ocean. Based on their linguistic similarity, this linguistic family included Malayo-Polynesians and Taiwan aborigines. The linguistic similarity also led to the controversial hypothesis that Taiwan is the homeland of all the Malayo-Polynesians, a hypothesis that has been debated by ethnologists, linguists, archaeologists, and geneticists. It is well accepted that the Eastern Austronesians (Micronesians and Polynesians) derived from the Western Austronesians (Island Southeast Asians and Taiwanese), and that the Daic populations on the mainland are supposed to be the headstream of all the Austronesian populations.ResultsIn this report, we studied 20 SNPs and 7 STRs in the non-recombining region of the 1,509 Y chromosomes from 30 China Daic populations, 23 Indonesian and Vietnam Malayo-Polynesian populations, and 11 Taiwan aboriginal populations. These three groups show many resemblances in paternal lineages. Admixture analyses demonstrated that the Daic populations are hardly influenced by Han Chinese genetically, and that they make up the largest proportion of Indonesians. Most of the population samples contain a high frequency of haplogroup O1a-M119, which is nearly absent in other ethnic families. The STR network of haplogroup O1a* illustrated that Indonesian lineages did not derive from Taiwan aborigines as linguistic studies suggest, but from Daic populations.ConclusionWe show that, in contrast to the Taiwan homeland hypothesis, the Island Southeast Asians do not have a Taiwan origin based on their paternal lineages. Furthermore, we show that both Taiwan aborigines and Indonesians likely derived from the Daic populations based on their paternal lineages. These two populations seem to have evolved independently of each other. Our results indicate that a super-phylum, which includes Taiwan aborigines, Daic, and Malayo-Polynesians, is genetically educible.

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Cyclooxygenase-2 (COX-2) plays an important role in rheumatoid arthritis and therefore, has been a major target for anti-arthritis therapies. The expression of COX-2 is induced by inflammatory cytokines such as TNF-alpha and IL-1beta, and inhibited by glucocorticoids. However, the molecular mechanisms underlying the anti-inflammatory and immune suppressive actions of glucocorticoids are not well defined. Here we report that glucocorticoid-induced leucine zipper (GILZ) mimics glucocorticoid action and inhibits inflammatory cytokine-induced COX-2 expression in bone marrow mesenchymal stem cells, the cells that have been recently implicated in the pathogenesis and progression of rheumatoid arthritis. Using a retrovirus-mediated gene expression approach we demonstrate that overexpression of GILZ inhibits TNF-alpha and IL-1beta-induced COX-2 mRNA and protein expression, and knockdown of GILZ by shRNA reduces glucocorticoid inhibition of cytokine-induced COX-2 expression. Consistent to these results, overexpression of GILZ also inhibits NF-kappaB-mediated COX-2 promoter activity. Finally, we show that GILZ inhibits COX-2 expression by blocking NF-kappaB nuclear translocation. Our results suggest that GILZ is a key glucocorticoid effect mediator and that GILZ may have therapeutic value for novel anti-inflammation therapies.

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Several diet and lifestyle factors associated with CP/CPPS and pain severity were determined in this study. These modifiable conditions are potential targets for treatment of CP/CPPS. However, further studies are necessary to determine their role in the pathogenesis of CP/CPPS.

Background:The in vivo role of GILZ, a glucocorticoid-indicible protein, in bone acquisition is unknown. Results: Overexpression of GILZ in osteoprogenitor cells increases bone acquisition in mice. Conclusion: GILZ enhances bone acquisition by promoting marrow mesenchymal stem/progenitor cell osteogenic differentiation. Significance: GILZ may represent the first GC-responsive gene mediating the positive effect of GCs in bone.