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Effects Of αD3 On The Expression Of RANK/RANKL/OPG In Aged Male Rats

Posted on:2011-03-21Degree:DoctorType:Dissertation
Country:ChinaCandidate:X W ZhouFull Text:PDF
GTID:1114360305493027Subject:Surgery
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BackgroundOsteoporosis is an aged-related metabolic diseases characterized with decrease in mass and increase in fracture. The rank/rank/opg system is regarded as the most important mechanism in regulating the differentiation of osteoclast. It is also taken as the fundamental reason for systemic osteoporosis.But it is uncertain whether rank/rank/opg systems start the maxillofacial osteoporosis and the relationship between this system and bone mineral density. Female osteoporosis has been paid much attention because of the deformity of estrogen, but the male osteoporosis is becoming a serious world problem with the aged society. The deformity of androgen is an important reason for male osteoporosis,femur Maxillofacial osteoporosis contribute to face depression and flexible teeth as well as alveolar atrophy and brings chewing and pronunciation and beauty problems.Reconstruction is due to fail because little bone tissue can be used to support the prosthesis.To find an effective medicine to increase the bone mass is an urgent problem that should be solved in clinical practice.As a basic medicine for osteoporosis whether VitD could be used for maxillofacial osteoporosis is unknown. So it is necessary to establish a male rat model to clarify the effects of androgen on the bone mineral density and bone mass and to investigate whether the rank/rankl/opg system start the maxillofacial osteoporosis.It is also necessary to observe the effects of alfacalcidol on mandible of aged ratsObjective:To investigate the expression levels of receptor activator of NF-kB ligand (rankl)and osteoprotegerin(opg)mRNA in mandible of different age man.Method:Between May 2008 and January 2009,bone tissues of the mandible were collected as the experimental material from 46 patients suffering from jaw facial deformity and extraction.The patients with periodontist, systemic disorder and smoking as well as drinking were excluded.They were divided into three groups.young group,whose age was 10-29years old;middle age groups,whose age was 30-59 years old;aged groups,whose age was 60-89years old.The expression levels of RANKLmRNA and OPGmRNA were examined by real-time quantitative.Results:1,Compared with young group, rankl mRNA levels in mandible were 2.1-fold and 5.3-fold higher in middle age and aged group,respectively,whereas OPGmRNA were3.3-fold and 4.8-fold higher in middle age and aged group,respectively.2,Rankl and opg are positively corrected with age.Conclusions:1,The expression of rankl and opg is increasing with age greatly.2,The bone reconstruction of mandible is activated in middle aged group.The formation is over absorption.3,The reconstruction of mandible in aged group is at low transform.The absorption is over information. Objective:To investigate the aged-related changes of biochemical mark and bone mineral density as well as bone histomorphology in rats and to disscuss the effects of a D3 on aged rats.Methods:Sixty male Wistar rats with different age were divided into four groups:groupA,6-week-old male wistar rat;groupB,6-month-old male wistar rat;groupC,24-month-old male wistar rat;groupD24-month-old male wistar rat.Group D was treated with a D3 three times a week for 10 weeks at a does of0.05ug/kg/d-1 body weight by gastric feeding.The blood samples were collected for determination of biochemistry parameters. The left femur and mandible were collected for dual energy x-ray absorptionmetry and histomorphology.Result:Biochemistry indices:1,Testosterone decreased significantly with age.There is no significant difference among groups.2,Compared with 6 weeks group,6 months and 24months group as well as a D3 group are followed by a decrease in ALP and BGP with age. 3,TRACP5b is increased with age.There is significant difference between aged group and 6months group.4,Bone gla protein has positive relationship with alkaline phosphatase and negative relationship with tartrate-resistant acid phosphatase 5b.5,Little changes has been found in calcium and phosphorus among groups.Bone mineral density:1,Bone mineral density is increased with age in femur and mandible.2,Bone mineral density is higher in a D3 group than that in 24 months group. There is no significant difference among groups.Histomorphology:1,Trabecular thickness and areas are increased with age in femur and mandible.2,The numerber of osteoclast in mandible of 6 weeks group is higher than the other three groups,while in femur 6 months group is higher than the other three groups.3,Compared with 6 months group, the trabecular thickness of 24 months group is increased by 53%, while trabecular separation is increased 123%.4,Trabecular area of a D3 group is increased by 33% compared with 24 months group.Conclusions:1,Testosterone is decreased dramatically with age.2,The biochemistry indices of bone formation is decreased and absorption is increased with age.3,The formation and absorption are at low status in aged groups.4,Alfacalcidol has the effects to promote the bone mass of mandible.Objective:To investigate the expression of RANK/RANKL/OPG in mandible and femur and to discuss the relationship between systemic osteoporosis and mandible as well as the effects of a D3 on the expression of rankl and opg in aged rats.Methods The left proximal of femur and mandible were collected to investigate the expression of rank/rankl/opg by RT-PCR and immunohistochemistry. Results:RT-PCR of femur1,The expression of rankl mRNA in femur were 6.2-fold and 7.3-fold higher in 6 months group and aged group, respectively,compared with 6 weeks group, while OPGmRNA levels is increased with age slightly.2,Alfacalidol groups presented a higher mean expression of rankl and opg and a significantly lower mean expression of rank than did control subjects.3,The ratio of RANKL/OPG is increased with age in femur. The ratio of RANKL/OPG in 6months and 24 months group as well as a D3 groups are obviously higher than that in 6 weeks group.RT-PCR of mandible1,The expression of rankl mRNA in mandible were 6.1-fold and 6.4-fold higher in 6 months group and aged group, respectively, compared with 6 week group.2,Compared with 6 months group the ratio of RANKL/OPG in24 months groups is decreased.3,The expression of rankl mRNA and the OPG mRNA is increased slightly in a D3 group compared with 24 months group, while the expression of rank is decreased obviously.Immunohistochemical1,Rankl and opg were co-localized in the osteoblast and chondrocytes. 2,The expression of opg mRNA in mandible and femur in 6 weeks group is higher than that in 6 months group.3,The expression of opg mRNA is obvious in alfacalcidol group compared with 24 months group.Conclusion:1,The expression of rankl mRNA is increased dramatically with age, while opg mRNA is increased slightly. The ratio of rankl/opg mRNA is also increased with age,promote the osteoclast activity and bone turnover.2,Compared with 6 months group,the expression of opg mRNA in 6 weeks group is higher than that in 6 months group.This is the difference between mandible and femur.3,The co-expression of OPG and RANKL in the same bone cell types confirms their strictly coupled action in the regulation of bone metabolism.4,Alfacalcidol favor increased formation over resorption both in mandible and femur.5,Bone gla protein has negative relationship with rankl and the ratio of rankl/opg in femur and negative relationship with rankl in mandible.
Keywords/Search Tags:mandible, male, osteoprotegerin, receptor activated nuclear factor kappa B ligand, bone mineral density, histomorphology, biochemistry indices, mandible, femur, osteoprotegerin, receptor activated nuclear factor kappa B ligand
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