From Hair to Heart: Hair-Follicle-Associated Pluripotent (HAP) Stem Cells Can Simultaneously Differentiate Into Mature Cardiomyocytes and Atrial Myocytes

Hair-follicle-associated pluripotent (HAP) stem cells express nestin, and are located in the bulge area of hair follicles and can differentiate to numerous types of cells. In the present study, we demonstrate that rat HAP stem cells simultaneously differentiated to mature cardiomyocytes and atrial myocytes. The addition of isoproterenol, activin A, bone morphogenetic protein 4 (BMP 4), basic fibroblast growth factor (bFGF), and cyclosporin A (CSA), induced simultaneously differentiation of HAP stem cells to c-kit-positive cardiomyocytes and MLC-2a-expressing atrial myocytes. The results of the present study suggest that HAP stem cells differentiating to cardiomyocytes and atrial myocytes have future clinical potential for heart regeneration.

Bone Morphogenetic Protein 4 Alleviates DSS-Induced Ulcerative Colitis Through Activating Intestinal Stem Cell by Target ID3

Damage to intestinal epithelial cell proliferation or intestinal stem cell (ISC) maintenance may trigger inflammatory bowel disease (IBD), and protecting the ISCs is critical for IBD treatment. Here, we found that in the dextran sulfate sodium (DSS)-induced ulcerative colitis mice model, colon epithelium and Lgr5+ intestinal stem cells (ISCs) renew quickly during the first 3 days. We also found that during this renewing period, SMAD4 and bone morphogenetic protein 4 (BMP4) expression were significantly upregulated. An extra BMP4 treatment could preserve the Lgr5+ ISCs and the colon epithelium turnover, and could significantly decrease colon mucosal damage. Moreover, we found that BMP4 regulated ID3 expression in the colon epithelium. Depletion of ID3 could significantly reduce the epithelium renewal and ratio of Lgr5+ ISCs at the base of crypts. In conclusion, the present study showed that BMP4 could maintain epithelium cellular proliferation and the ISCs function through ID3 in mice with DSS-induced colitis. The administration of exogenous BMP4 supplement could alleviate DSS-induced colitis by restoring epithelium cellular proliferation and ISC function, suggesting the possible therapeutic function of BMP4 for ulcerative colitis.

Decreased Thrombospondin-1 and Bone Morphogenetic Protein-4 Serum Levels as Potential Indices of Advanced Stage Lung Cancer

Introduction: Lung cancer belongs to the most common carcinoma worldwide and is the leading cause of cancer-related death. Bone morphogenetic protein-4 (BMP-4) is extracellular signaling molecule involved in many important processes, including cell proliferation and mobility, apoptosis and angiogenesis. Thrombospondin-1 (TSP-1) belongs to the extracellular matrix proteins. It participates in the cell-to-cell and cell-to-matrix interactions and thus plays important role in tumor microenvironment for cancer development and metastasis formation. Aim: To investigate serum levels of TSP-1 and BMP-4 together with BMP-4 polymorphism in lung cancer patients. Material and Methods: A total of 111 patients (76 men) with newly diagnosed lung cancer, including 102 patients with non-small cell lung cancer and 9 patients with small-cell lung cancer. Advanced stage of lung cancer was diagnosed in 99 (89%) of patients: stage IV—in 48, stage IIIB—in 33, stage IIIA—in 18 patients; there were six patients with stage II and six patients with stage I. The control group consisted of 61 healthy persons. In all the subjects, serum levels of BMP-4 and TSP-1 were measured by ELISA. With a Real-Time PCR system genotyping of BMP-4 was performed. Results: BMP-4 and TSP-1 serum levels were significantly lower in the patients with lung cancer than in the controls (TSP-1:10,109.2 ± 9581 ng/mL vs. 11,415.09 ± 9781 ng/mL, p < 0.05; BMP-4: 138.35 ± 62.59 pg/mL vs. 226.68 ± 135.86 pg/mL p < 0.001). In lung cancer patients TSP-1 levels were lower in advanced stages (9282.07 ± 4900.78 ng/mL in the stages III-IV vs. 16,933.60 ± 6299.02 ng/mL in the stages I-II, p < 0.05) and in the patients with than without lymph nodes involvement (10,000.13 ± 9021.41 ng/mL vs. 18,497.75 ± 12,548.25 ng/mL, p = 0.01). There was no correlation between TSP-1 and BMP-4 serum levels. BMP-4 gene polymorphism did not influence the results of the study. Conclusion: Decreased levels of TSP-1 and BMP-4 may serve as potential indices of lung cancer, with additional importance of low TSP-1 level as a marker of advanced stage of the disease.

Identification of bone morphogenetic protein 4 in the saliva after the placement of fixed orthodontic appliance

Background This study was conducted in order to explore the effects of orthodontic tooth movement (OTM) on the changes of salivary proteome. This prospective observational pilot study recruited 12 healthy teenage boys with malocclusion treated with a fixed orthodontic appliance and 6 appropriate control participants. Saliva samples were collected a day before and at 0, 2, 7, and 30 days after initialization of treatment, corresponding to the initial, lag, and post-lag phases of OTM. Pooled samples were analyzed by liquid chromatography-mass spectrometry, ELISA, and Western blotting. To date, there is no published data on the presence of BMP molecules or their antagonists in the saliva or in the gingival cervical fluid related to orthodontic conditions. Results A total of 198 identified saliva proteins were classified based on their functional characteristics. Proteins involved in bone remodeling were observed exclusively 30 days post appliance placement, including bone morphogenetic protein 4 (BMP4), a BMP antagonist BMP-binding endothelial regulator, insulin-like growth factor-binding protein 3, cytoskeleton-associated protein 4, and fibroblast growth factor 5. Based on the analysis of protein interactions, BMP4 was found to have a central position in this OTM-related protein network. Conclusions The placement of a fixed orthodontic appliance induced occurrence of proteins involved in bone remodeling in the saliva at a time corresponding to the post-lag period of OTM. Limitations of this study include a relatively small sample size, limited time of monitoring patients, and the lack of interindividual variability assessment.