| Background and Purposes KBD(Kashin-Beck disease, KBD) is a chronic, endemic, Paget joint disease, high morbidity, serious harm to people’s health. Our country used to make KBD as the Ministry of Health "Plan", the national "Plan" and "eight five" scientific and technological projects. However, KBD pathogenesis is unclear, it is presumed cause of material injury in the body and how deep chondrocytes, evidence has not been obtained,we can not explain the pathoggenecrosis associated with oxidative stress, the development of KBD is based on the oxidatenesis of deep KBD cartilagenecrosis so far. Our preliminary findings, KBD cartilaion caused by free radicals stress injury as the core of the pathological process. KBD chondronecrosis infringement epiphyseal growth plate and articular cartilage chondrocytes deep mainly because of the special organizational structure of hyaline cartilage in the study at home and abroad, as long as involving joint and epiphyseal cartilage lesions hypertrophic layer, it always focus on chondrocytes differentiation regulation.Fibroblast growth factor 8(Fibroblast Growth Factor 8, FGF8) That is a kind of androgen-dependent mouse breast cancer cell line isolated in SC3 in the 1990 s by foreign scholars who find out, it is also known as androgen-induced growth factor(androgen induced growth factor, AIFGF). Human fibroblast growth factor-8 is composed of 233 amino acids(molecular weight of about 26 kDa) of the basic protein isoelectric point of about 105 potential. From its early cell differentiation in a pivotal role, with the skull and the brain and skeletal limbs and so formed are closely linked, it grows from one fertilized egg to embryo and growth factor in this process is indispensable. Fibroblast growth factor receptor 3(Fibroblast Growth Factor Receptor 3, FGFR3) belongs to a class of protein tyrosine kinases(receptor tyrosine kinase, RTK). We have found four fibroblast growth factor receptor so far, FGFR1, FGFR2, FGFR3, FGFR4. They have between 55% to 72% identity at the amino acid level. Through previous studies we know that the fibroblast growth factor receptor 3 signaling pathway in cartilage development, reconstruction and bone diseases are closely linked. From fibroblast growth factor receptor 1, 2, or loss of function mutations cause enhanced to include craniosynostosis(craniosynostosis, CS), achondroplasia(achondroplasia, ACH) and CATSHL(camptodactyly, tall stature, scoliosis, a variety of human skeletal system genetic disease and hearing loss), including syndrome. In previous studies which have been reported found in the KBD cartilage into bone disorder incidents involving terminally differentiated chondrocytes deep process of abnormal differentiation,such as fibroblast growth factor, parathyroid hormone related peptide(Parathyroid Hormone related Peptide, PTHrp), transforming growth factor-β expression and other abnormalities, but these abnormal expression of differentiation factors and the relationship between terminally differentiated chondrocytes in cartilage disorder and KBD deep study caused no deaths.This study is intended to oxidative stress induced chondrocyte differentiation dysregulation as a starting point, by detecting a fibroblast growth factor receptor 3 and 8 expression in abnormal chondrocyte differentiation as a mediated,aim to analyze the KBD relationship between patients and preliminary study FGF and FGFR biological functions in the occurrence of KBD, trying to reveal the pathogenesis of deep KBD cartilage necrosis, thus providing a theoretical basis for further research to clarify the etiology and prevention of KBD.Methods This study uses Real Time quantitative PCR, Western Blotting and immunohistoch emical technique methods, such as screening abnormal cartilage differentiation related regulating differentiation factor- fibroblast growth factor and its receptor, detection in KBD children and expression level of animal model of cartilage, research on the etiology and pathogenesis of KBD provides new train of thought.Statistical methods: test is mainly used for patients with kaschin-beck group and normal control group of FGF and FGFR positive expression in immunohistochemical level difference comparison; Chi-square test is mainly used for high expression and low expression group FGF and FGFR diff on mRNA level and protein level.Results 1. Each SIN-1 concentration gradient under the induction of articular cartilage hypertrophy cells in mice mRNA and protein expression level of FGF8 and FGFR3 have significant difference, statistically significant difference(p < 0.05).And induce hypertrophy of articular cartilage cells in mice to the successed control group, SIN-10 mmol group, FGF8 and FGFR3 expression quantity to increase, especially in the mice ADTC5 cartilage cell lines.2. Under the condition of low selenium and T-2 toxin, the four groups of SD rats induced by kashin-beck model of fresh tissue protein and paraffin pathological detection of abnormal expression of FGF8 and FGFR3 expression level, four groups of model organization protein expression levels have significant difference, statistically significant difference(p < 0.05); Four groups of models of paraffin pathological positive rate have significant difference, statistically significant difference(p < 0.05).Compared with normal group, low selenium group, T-2 group, the low selenium + T-2 groups of FGF8 and FGFR3 expression levels is rise.3. Using immune histochemical methods examined 64 cases paraffin embedding cartilage for FGF8 and FGFR3 gene expression, found in children kaschin-beck disease finger articular cartilage and adult articular cartilage in KBD patients, FGF8 and FGFR3 protein expression mainly in the cytoplasm, and the case group and control group of FGF8 and FGFR3 positive expression rate have significant difference, statistically significant difference(p < 0.05).4. ConclusionFGF8 and FGFR3 play an important role in the kaschin-beck disease, the increase in the expression of FGF8 and FGFR3 may cause kashin-beck articular cartilage differentiation disorder. |
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