Smoking affects mRNA expression of bone morphogenetic proteins in human periosteum.

Periosteum is important for bone homoeostasis through the release of bone morphogenetic proteins (BMPs) and their effect on osteoprogenitor cells. Smoking has an adverse effect on fracture healing and bone regeneration. The aim of this study was to evaluate the effect of smoking on the expression of the BMPs of human periosteum. Real-time polymerase chain reaction was performed for BMP-2,-4,-6,-7 gene expression in periosteal samples obtained from 45 fractured bones (19 smokers, 26 non-smokers) and 60 non-fractured bones (21 smokers, 39 non-smokers). A hierarchical model of BMP gene expression (BMP-2 > BMP-6 > BMP-4 > BMP-7) was demonstrated in all samples. When smokers and non-smokers were compared, a remarkable reduction in the gene expression of BMP-2, -4 and -6 was noticed in smokers. The comparison of fracture and non-fracture groups demonstrated a higher gene expression of BMP-2, -4 and -7 in the non-fracture samples. Within the subgroups (fracture and non-fracture), BMP gene expression in smokers was either lower but without statistical significance in the majority of BMPs, or similar to that in non-smokers with regard to BMP-4 in fracture and BMP-7 in non-fracture samples. In smokers, BMP gene expression of human periosteum was reduced, demonstrating the effect of smoking at the molecular level by reduction of mRNA transcription of periosteal BMPs. Among the BMPs studied, BMP-2 gene expression was significantly higher, highlighting its role in bone homoeostasis.

Predictive role of cytokine gene polymorphisms for the development of femoral head osteonecrosis.

INTRODUCTION: Osteonecrosis (ON) is a multifactorial disease that leads to hip destruction. Lately, much focus has been at femoral head preservation with nonsurgical methods. In this study we examined the polymorphisms of IL-1α, IL-1R, IL-1RA, IL-4Rα, IL-1ß, IL-12, γIFN, TGF-ß, TNF-a, IL-2, IL-4, IL-6 and IL-10 genes for evaluation of their contribution in ON. MATERIAL AND METHODS: DNA was extracted from 112 ON patients and 438 healthy donors. Analysis of the polymorphisms was completed using the PCR-SSP method. Statistical analysis was performed using the χ ^{2} test to compare the genotype and allelic frequency distribution. RESULTS: The CT and GA genotypes of the IL-1α (-889) and TNF-a (-238) genes were found higher in the patients (51.8% and 10.8%, respectively) compared to the healthy donors (39.7% and 2.1%, respectively). In TGF-ß codon 25, the G to C polymorphism in the homozygous state was found in 1.8% of the patients and the C allele frequency was 8.9%, whereas the G allele frequency was 91.1%. Also, at the IL-10 (-1082) gene the GG genotype was 16.2% in the controls whereas in the patients was 7.2%. CONCLUSIONS: Based on the above, we showed that certain genotypes of the IL-1α, TGF-ß, IL-10 and TNF-a genes could be related in the pathogenesis of a complicated disease, such as osteonecrosis. The presence of one of the above mentioned polymorphisms or the simultaneous carriage of more than one may further increase the risk for osteonecrosis, especially in those at high risk, such as patients receiving corticosteroids.