Effects of recombinant human bone morphogenic protein-2 and human bone marrow-derived stromal cells on in vivo bone regeneration of chitosan-poly(ethylene oxide) hydrogel.

In vivo bone regeneration of chitosan-poly(ethylene oxide) (PEO) hydrogel in rat carlvarial defects was evaluated by using both human bone marrow-derived stromal cells (hMSCs) and recombinant human bone marrow protein-2 (rhBMP-2) for 4 and 8 weeks. In situ chitosan-PEO hydrogel was fabricated by mixing the precursor solutions of both chitosan-acrylate and PEO-thiol. Fabrication of the injectable hydrogels was modulated from within a minute to hours by controlling the temperature and pHs of the precursor solution. Gel swellings were dependent on the conditions of pHs and temperatures of the precursor solutions, showing higher gel swelling in basic water than in either acidic or neutral water. The compression strengths and in vitro degradation of hydrogels were also evaluated by controlling the concentrations of both precursor solutions and lysozyme, respectively, by referencing to the morphology of the control hydrogel with no enzyme added. Hydrogels showed sustained release of rhodamine-B over time. After implantation of the injectable hydrogels in rat calvarial defects for 4 and 8 weeks, in vivo bone regenerations were compared with by evaluating the degrees of new bone formations with Soft X-ray, microcomputed tomography, and histological stainings of hematoxylin and eosine Y and Masson's trichrome. Degrees of in vivo bone regeneration were controlled by encapsulating in advance either hMSCs, rhBMP-2, or both in the precursor solutions of the hydrogel. The defect implanted with hydrogel only showed higher amount of bone tissue regeneration than that of the control defect site. The defect sites with hydrogel containing both hMSCs and rhBMP-2 demonstrated highest amount of bone tissue regeneration among the samples.

Association of 5-hydroxytryptamine (serotonin) receptor 4 (5-HTR4) gene polymorphisms with asthma.

BACKGROUND AND OBJECTIVE: The neurotransmitter, 5-hydroxytryptamine, acts as an immunomodulator by stimulating the release of inflammatory cytokines and regulating the function of dendritic cells and monocytes. The 5-hydroxytryptamine receptor 4 (HTR4) gene is located in a region previously linked to an increased risk of asthma and atopy. The aim of this study was to investigate the association between HTR4 and asthma. METHODS: Thirty-two single nucleotide polymorphisms (SNP) in HTR4 were investigated by direct sequencing of 24 DNA samples from unrelated Korean subjects. RESULTS: The 32 genetic variants comprised 22 intronic SNP, two SNP in the 3'-untranslated region (exon 7) and eight SNP in the 3'-downstream region. Logistic regression analysis showed that two intronic polymorphisms were significantly associated with the risk of asthma. Two minor HTR4 alleles, +142828G>A and +122769G>A, occurred at significantly higher frequencies in the asthmatic group than in the healthy control group (49.59% vs 42.29%, P=0.003, and 47.99% vs 40.35%, P=0.008, respectively), and these differences remained significant after correction for multiple testing (P=0.05, dominant mode of inheritance; and P=0.03, dominant mode, respectively). Haplotype analysis revealed three haplotype blocks. The frequency of haplotype 1 in block 2 was significantly higher in asthmatics (P=0.003, dominant mode), whereas the frequency of haplotype 4 in block 3 was significantly lower in asthmatics (P=0.0009, dominant mode). CONCLUSIONS: SNP and haplotypes of the HTR4 gene were associated with the asthma phenotype and genetic variation of HTR4 may affect susceptibility to the development of asthma.