Suppression of discoidin domain receptor 1 expression enhances the chondrogenesis of adipose-derived stem cells.

Effectively directing the chondrogenesis of adipose-derived stem cells (ADSCs) to engineer articular cartilage represents an important challenge in ADSC-based articular cartilage tissue engineering. The discoidin domain receptor 1 (DDR1) has been shown to affect cartilage homeostasis; however, little is known about the roles of DDR1 in ADSC chondrogenesis. In this study, we used the three-dimensional culture pellet culture model system with chondrogenic induction to investigate the roles of DDR1 in the chondrogenic differentiation of human ADSCs (hADSCs). Real-time polymerase chain reaction and Western blot were used to detect the expression of DDRs and chondrogenic genes. Sulfated glycosaminoglycan (sGAG) was detected by Alcian blue and dimethylmethylene blue (DMMB) assays. Terminal deoxy-nucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining was used to assess cell death. During the chondrogenesis of hADSCs, the expression of DDR1 but not DDR2 was significantly elevated. The depletion of DDR1 expression in hADSCs using short hairpin RNA increased the expression of chondrogenic genes (SOX-9, collagen type II, and aggrecan) and cartilaginous matrix deposition (collagen type II and sGAG) and only slightly increased cell death (2-8%). DDR1 overexpression in hADSCs decreased the expression of chondrogenic genes (SOX-9, collagen type II, and aggrecan) and sGAG and enhanced hADSC survival. Moreover, DDR1-depleted hADSCs showed decreased expression of the terminal differentiation genes runt-related transcription factor 2 (Runx2) and matrix metalloproteinase 13 (MMP-13). These results suggest that DDR1 suppression may enhance ADSC chondrogenesis by enhancing the expression of chondrogenic genes and cartilaginous matrix deposition. We proposed that the suppression of DDR1 in ADSCs may be a candidate strategy of genetic modification to optimize ADSC-based articular cartilage tissue engineering.

Absence of endemic measles transmission in a highly vaccinated population from 1999 to 2008: implications of sustained measles elimination in Taiwan.

BACKGROUND: Measles remains a leading vaccine-preventable cause of child mortality worldwide. The impact of vaccination programs can be seen in the increasingly low incidence of measles. However, cases of measles continue to occur in low numbers every year in Taiwan. We assessed the epidemiology of measles in Taiwan from 1999 to 2008 with a focus on domestic versus imported cases. METHODS: We analyzed the data reported to surveillance systems at the Taiwan Center for Disease Control, where viral isolation was performed. RESULTS: A total of 84 measles cases were reported from 1999 to 2008 in Taiwan with the incidence of measles varying from 0 to 1.5 per 1,000,000 people per year, peaking in 2002 and again in 2008. The incidence decreased with increasing age in both males and females. Among the 84 reported measles cases, 39 (46%) originated internationally, 8 (10%) were epidemiologically linked to imported cases and the source was unknown in 37 (44%) of the cases. The unknown-source cases were analyzed for potential evidence of endemic measles transmission. Most of the measles cases that occurred in Taiwan from 1999 to 2008 were associated with imported cases. No endemic transmission of measles in Taiwan was identified. CONCLUSIONS: This study suggests that maintaining the high rate of vaccination coverage is needed to prevent future outbreak and sustain the elimination of measles in Taiwan.