Current and future uses of skeletal stem cells for bone regeneration.

The postnatal skeleton undergoes growth, modeling, and remodeling. The human skeleton is a composite of diverse tissue types, including bone, cartilage, fat, fibroblasts, nerves, blood vessels, and hematopoietic cells. Fracture nonunion and bone defects are among the most challenging clinical problems in orthopedic trauma. The incidence of nonunion or bone defects following fractures is increasing. Stem and progenitor cells mediate homeostasis and regeneration in postnatal tissue, including bone tissue. As multipotent stem cells, skeletal stem cells (SSCs) have a strong effect on the growth, differentiation, and repair of bone regeneration. In recent years, a number of important studies have characterized the hierarchy, differential potential, and bone formation of SSCs. Here, we describe studies on and applications of SSCs and/or mesenchymal stem cells for bone regeneration.

Emodin ameliorates cartilage degradation in osteoarthritis by inhibiting NF-κB and Wnt/ß-catenin signaling in-vitro and in-vivo.

The overproduction of MMPs (matrix metalloproteinases) and members of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) protein family plays an important role in the pathogenesis of osteoarthritis (OA). The potential of selective MMPs or ADAMTS inhibitors as chemopreventive agents for OA has been demonstrated in several studies. In this study, we investigated the protective effects of emodin (1,3,8-trihydroxy-6-methylanthaquinone), isolated from the root of Rheum palmatum L., in the inhibition of MMP and ADAMTS expression in both rat chondrocytes and an animal model of OA. The expression of MMP-3, MMP-13, ADAMTS-4, ADAMTS-5, aggrecan, and collagen II mRNA and protein in interleukin-1beta (IL-1ß)-induced rat chondrocytes was followed by quantitative real-time PCR and western blot. The activation of the NF-κB and Wnt/ß-catenin pathways by IL-1ß was assessed by western blot. The in vivo effects of emodin were evaluated by intra-articular injection in rats in an experimental model of OA induced by anterior cruciate ligament transection. Emodin dose-dependently down-regulated the expression of MMP-3, MMP-13, ADAMTS-4 and ADAMTS-5 at both the mRNA and protein level in IL-1ß-stimulated rat chondrocytes. In addition, the IL-1ß-induced activation of NF-κB and Wnt signals was attenuated by emodin, as determined by western blotting. The intra-articular injection of emodin in a rat OA model ameliorated OA progression, as determined in morphological and histological analyses in vivo. Taken together, our findings demonstrate that emodin is a promising therapeutic agent for the prevention and treatment of OA.

[DNA vaccine encoding SjIR3 induces partial immune protection against Schistosoma japonicum in mice].

OBJECTIVE: To detect the protection in mice induced by DNA vaccine encoding SjIR3 against Schistosoma japonicum (Sj). METHODS: Sj1R3 was amplified by PCR with specific primers and linked to T vector. The reconstructed plasmid was digested by Xho I and BamH I. The target segments were collected and inserted into pcDNA3.0 to construct DNA vaccine SjIR3/pC. Fifty-four female mice were divided into 3 groups: groups A and B received normal saline and pcDNA3.0 respectively as controls, and group C was immunized with SjIR3/pC. All the mice were injected three times with an interval of two weeks. Sera were collected before each inoculation and before challenge infection. Six mice from each group were sacrificed 2 weeks after the final inoculation and spleen cells were collected. Serum IgG was detected by ELISA and the proliferation activity of spleen T lymphocytes induced by ConA or rSjIR3 was detected by MTT assay. The remaining mice were infected by (40+/-1) Sj cercariae per mouse 2 weeks after the final inoculation. Forty-five days later, mice were sacrificed and perfused, numbers of adult worms and of eggs in liver tissue were counted. RESULTS: ELISA showed no significant change of serum IgG level in groups A and B, but considerable increase in group C (0.78+/-0.05) (P<0.01). The proliferation activity of spleen T lymphocytes increased with the induction of ConA or recombinant protein rSjIR3 after the final inoculation. The A570 was 0.57+/-0.02 and 0.68+/-0.01 respectively, showing a significant difference in comparison to the groups A and B (P<0.01). The worm reduction rate and the egg reduction rate in group C were 29.42% and 36.56% respectively. CONCLUSION: DNA vaccine encoding SjIR3 induces humoral and cell-mediated immune response, and shows partial immune protection against Schistosoma japonicum.