Background
During bone fracture repair, mesenchymal stem cells (MSC) differentiate into chondrocytes and osteoblasts to form a fracture callus. Our laboratory previously reported that alcohol‐exposed rodents with a surgically created tibia fracture display deficient fracture callus formation and diminished signs of endochondral ossification characterized by the absence of chondrocytes and mature hypertrophic chondrocytes, suggesting that alcohol may inhibit MSC differentiation. These findings led to our hypothesis that alcohol exposure inhibits mesenchymal stem cell chondrogenic differentiation within the developing fracture callus.
Methods
In the present study, we utilized a lineage‐tracing approach to determine which stage(s) of chondrogenic differentiation are affected by alcohol exposure. We utilized lineage‐specific reporter mice to determine the effects of alcohol on MSC and early and late chondrogenic cell frequencies within the fracture callus. In addition, serially sectioned slides were stained immunofluorescently and immunohistochemically and quantified to determine the effect of alcohol on cell proliferation and apoptosis, respectively, within the fracture callus of alcohol‐administered rodents.
Results
Alcohol‐administered rodents had a reduced fracture callus area at 4, 6, and 9 days postfracture. Alcohol had no effect on apoptosis in the fracture callus at any of the examined timepoints. Alcohol‐administered rodents had significantly fewer proliferative cells in the fracture callus at 9 days postfracture, but no effect on cell proliferation was observed at earlier fracture callus timepoints. Alcohol‐administered rodents had reduced Collagen2a1‐ and Collagen10a1‐expressing cells in the developing fracture callus, suggesting that alcohol inhibits both early chondrogenic differentiation and later chondrocyte maturation during fracture callus development.
Conclusion
The data suggest that alcohol could affect normal fracture healing through the mitigation of MSC chondrogenic differentiation at the callus site.
An analysis of the rate of celibacy, under 2 criteria (at the ages of 30 and 40) among the offspring of consanguineous and non-consanguineous marriages did not show significant differences both among whites and non-whites (mulattoes and negroes), in a Central Brazilian region. There is, therefore, no evidence that rare recessive genes play an important role in determining in individuals of the investigated area some disturbance of behavioral pattern that would create a resistance or difficulty to marriage. Since the population which has been studied is subdivided into a number of relatively small and ‘simple’ isolates, it is suggested that a different situation may prevail in the large and ‘complex’ isolates of the large cities. The higher prevalence of female celibates older than 40 years, as compared to males, is probably due to the preferential emigration of males, a fact that characterizes the region.
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