Objective To investigate the role of bone morphogenetic protein 2 (BMP-2) combined with hypoxic microenvironment in chondrogenic phenotype differentiation of bone marrow mesenchymal stem cells (BMSCs) of rat in vitro. Methods BMSCs were harvested from 4-week-old female Sprague Dawley rats. BMSCs at passage 2 were divided into 4 groups according different culture conditions: normoxia control group (group A), normoxia and BMP-2 group (group B), hypoxia control group (3% oxygen, group C), and hypoxia and BMP-2 group (group D). Then the cellular morphology was observed under inverted phase contrast microscope. Alcian blue immunohistochemical staining was used to detect the glycosaminoglycans (GAG), Western blot to detect collagen type II and hypoxia-inducible factor 1α (HIF-1α), and RT-PCRto detect the expressions of chondrogenic related genes, osteogenic related genes, and hypoxia related genes. Results At 21 days after induction of BMP-2 and hypoxia (group D), BMSCs became round, cell density was significantly reduced, and lacuna-l ike cells were wrapped in cell matrix, while the changes were not observed in groups A, B, and C. Alcian blue staining in group D was significantly bluer than that in other groups, and staining became darker with induction time, and the cells were stained into pieces of deeply-stained blue at 21 days. Light staining was observed in the other groups at each time point. The expression level of collagen type II protein in group D was significantly higher than those in other groups (P lt; 0.05). HIF-1α protein expression levels of groups C and D were significantly higher than those of groups A and B (P lt; 0.05). The expressions of collagen II α1 (COL2 α1) and aggrecan mRNA (chondrogenic related genes) were highest in group D, while the expressions of COL1 α1, alkaline phosphatase, and runt-related transcri ption factor 2 mRNA (osteogenic related genes) were the highest in group B (P lt; 0.05). Compared with groups A and B, HIF-1α (hypoxic related genes) in groups C and D significantly increased (P lt; 0.05). Conclusion BMP-2 combined with hypoxia can induce differentiation of BMSCs into the chondrogenic phenotype, and inhibit osteoblast phenotype differentiation. HIF-1α is an important signaling molecule which is involved in the possible mechanism to promote chondrogenic differentiation process.
Objective To evaluate the efficacy and safety of traditional Chinese medicine(TCM) paste in treating chronic obstructive pulmonary disease (COPD) in stable stage. Methods We electronically searched databases including PubMed, EMbase, The Cochrane Library (Issue 12, 2016), VIP, WanFang Data, CNKI and CBM to collect randomized controlled trials (RCTs) regarding TCM paste in combination with conventional Western therapy versus Western therapy alone in treating stable COPD from inception to December 2016. Two reviewers independently screened literature, extracted data and assessed the risk of bias of the included studies. The meta-analysis was conducted by RevMan 5.3 software. Results A total of 9 RCTs involving 605 Chinese patients were included. The results of meta-analysis showed that: when compared with conventional Western medicine alone, TCM paste combined with the conventional Western medicine significantly improved clinical effective rate (RR=1.20, 95% CI 1.10 to 1.31,P<0.000 1), decreased SGRQ score (MD=–4.53, 95% CI –5.41 to –3.65,P<0.000 01) and CAT score (MD=–2.45, 95% CI –3.38 to –1.51,P<0.000 01), increased FEV1% (MD=3.80, 95% CI 0.40 to 7.20,P=0.03), and reduced the frequency of acute exacerbation (P<0.05). No serious adverse reaction occurred in both groups. Conclusion The current evidence shows that combination of TCM paste and conventional Western medicine may improve clinical effective rate, quality of life, increase FEV1%, and reduce the frequency of acute exacerbation in patients with stable COPD. Due to the limited quality and quantity of included studies, the above results are needed to verify by more studies.