Mesenchymal stromal cells (MSCs) derived from human bone marrow have capability to differentiate into cells of mesenchymal lineage. Especially, the differentiation capability towards osteogenic/chondrogenic cells is very well known. We have already used the patient's MSCs for the treatments of various patients who have osteoarthritis, bone necrosis and bone tumor. However, the proliferation and differentiation capability of the MSCs are variable and many cells lose their capabilities after several passages. With the aim of conferring higher capability on human bone marrow MSCs, we introduced the Sox2 gene into the cells and found that Sox2-expressing MSCs showed consistent proliferation and osteogenic capability in culture media containing basic fibroblast growth factor (bFGF) compared to control cells. We also found that Nanog-expressing cells even in the absence of bFGF had much higher capabilities for expansion and osteogenesis than control cells. Present paper describes our bone tissue engineering strategy and focuses on the importance of transcription factors for the function of MSCs.

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Periodontal disease has been recognized as local infectious disease, which becomes major cause of tooth loss in the adults. However, it is now being re-recognized as low-grade inflammatory disease exhibiting negative impact on the host. It is believed that severer form of periodontal disease is often seen in diabetic and/or obese subjects. This may be associated with chronic immuno-activation due to hyperadipocytokinemia as well as hyperglycemia. Severe periodontal inflammation, in turn, acts to evoke insulin resistance and to accelerate atherosclerotic changes. Therefore, the disease may accelerate the fatigue of pancreatic β-cells as well as vascular inflammation. Overall, the disease may promotes the aging itself. Because of these unwanted negative effects of the disease, it is very important to understand the molecular mechanisms as to why such small, local inflammation due to oral infectious disease is intensified to the levels of influencing our systemic health. Here in this mini-review, we discuss about the negative effects of periodontal disease on acceleration of aging.

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Recent large-scale association studies revealed new susceptibility genes to systemic lupus erythematosus (SLE) including IRF5, STAT4 and BLK. Association of these genes have been quickly replicated by many studies in multiple populations. In this minireview, we discuss our recent studies on the association of these genes with SLE in Japanese. Although association of these genes was replicated, notable differences were observed between Caucasian and Japanese populations.
In Japanese, IRF5 risk haplotype in the Caucasians carrying three functional polymorphisms (a single nucleotide polymorphism [SNP] at exon 1B splice site, 10 amino acid insertion/deletion, a SNP at poly A signal) is almost absent. However, another intron 1 SNP, which was not described in the Caucasians, was significantly associated with SLE in Japanese.
On the other hand, both the STAT4 intronic SNPs and C8orf13-BLK intergenic SNPs associated in Caucasians were similarly associated with SLE in Japanese. Moreover, because of higher population frequencies of the risk genotypes and higher odds ratios, the contribution of these genes appeared to be greater in the Japanese than in the Caucasians.
Although association of these genes with SLE is established, the molecular mechanisms of the association remain largely unknown. In addition, further studies are required to develop applications of the genetics information for clinical use. Genetics finally began to reveal new and reliable clues to gain insight into the pathogenesis of highly complicated disorders such as SLE.

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Spinal cord injuries result in devastating loss of function, because spinal cord of human beings never regenerates after injury. People believed in this dogma for a long time. There is an emerging hope for regeneration-based therapy of the damaged spinal cord due to the progress of neuroscience and regenerative medicine including stem cell biology. In this review, we have summarized recent studies aimed at the development of regeneration-based therapeutic approaches for spinal cord injuries, including therapy with transplantation of neural crest stem cells and induction of axonal regeneration, and the establishment of new method for evaluating injured and regenerated axonal fibers by MRI.

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A large amount of chromosomal DNA is actively degraded during some physiological contexts such as programmed cell death and definitive erythropoiesis. DNase II is an acid DNase, and localized in lysosomes. It is required to degrade DNA of apoptotic cells after macrophages engulf dying cells, and also to degrade the nuclear DNA expelled from erythroid precursor cells. In the fetal liver and thymus of the DNase II^-/- mice, there are many abnormal macrophages which carry numerous undigested DNA, and the macrophages constitutively produce IFN-β. DNase II^-/- mice die in feto due to severe anemia caused by the overproduction of IFN-β.
To analyze the physiological role of DNase II in adult stage, we established two mice lines : DNase II^-/- IFN-IR(type-I interferon receptor)^-/- mice and mice with an induced deletion of the DNase II gene. Here we show the two mice lines (referred to DNaseII deficient mice) develop a chronic polyarthritis resembling human rheumatoid arthritis (RA). Histology showed severe synovitis accompanied by pannus formation and bone erosion. A set of inflammatory cytokine such as IL-1, IL-6, and TNF-α genes was strongly activated in the affected joints of these mice. Macrophages in bone marrow and spleen accumulated undigested DNA. Both gene expression of TNF-α in bone marrow and concentration of TNF-α in serum were elevated in DNaseII deficient mice before the disease onset. The disease development was blocked by administration of neutralizing antibody against TNF-α or the loss of TNF-α gene indicating that TNF-α played an essential role for the arthritis caused by impaired DNA degradation. In contrast, Rag2 deficiency (thus lack of B cells and T cells) did not affect the onset of the disease. These results show the arthritis in DNaseII deficient mice is dependent of cytokines and innate immunity but independent of acquired immunity.
These findings add an evidence to the unique concept we have proposed: "If DNA is not properly degraded, DNA causes adverse effects to organisms." We suggest an unexpected possibility that impaired DNA degradation can cause arthritis. Abnormal activation of macrophages or innate immunity may trigger the arthritis in some cases of human RA. DNase II deficient mice which show well resembling characteristics with human RA will contribute to reveal the pathology and develop beneficial therapies in RA.

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