The Effects Of Estrogen Receptors And Clagen Type Ⅱ Gene Expression On Estrogen Replacement In Ovariectomized Rat Condylar Cartilage

Objective: There is strong evidence for an association between estradiol and condylarcartilage. This study investigated the role of estrogen in the metabolism oftemporomandibular cartilage. By applying different concentration of17β-estradiol(17β-E2) to ovariectomized (OVX) rats, the estrogen receptors(ER), Collagen type Ⅱ(CⅡ), MMP-13and TIMP-1were tested by using Real-time PCR and Western-blotanalysis, in order to provide a theoretical basis for the replacement therapy oftemporomandibular joint disorder (TMD).Methods:1.The TMD animal models were established by resecting bilateral ovariesof female SD rats, then the change of estrogen level was verified by testing the shapeand mature index of vaginal epithelium exfoliated cells.2. Different concentration of17β-E2were injected immediately or delayed, and the ERαand ERβ in rat condylarcartilage were tested by using Western-blot and Real-time PCR analysis subsequently.3.The mRNA expression level of CⅡ, MMP-13and TIMP-1in rat condylar cartilagewere tested by using Real-time PCR.Results:1.The maure index of vaginal epithelium exfoliated cells of OVX rats was180/12/8, indicating low levels of estrogen in vivo.2.ER, Collagen type Ⅱ, MMP-13and TIMP-1mRNA could maintain at the normal level when500ug/kg/day of17β-E2were supplemented immediately. Yet this was not the case when17β-E2were givendelayed.3.Both50ug/kg/day and5000ug/kg/day of17β-E2administration cansuppress the expression of ER, either in protein or mRNA level, and this inhibitoryeffect is more obvious in5000ug/kg/day group.4.Both50ug/kg/day and5000ug/kg/day of17β-E2administration can significant increase the mRNA level ofMMP-13, while decreasing the mRNA level of CⅡ and TIMP-1. This phenomenonis also more distinct in5000ug/kg/day group. Conclusion:1.The biological effects of ER depend on normal physiologicalconcentration and accurate period of estrogen secretion. Physiologic concentration of17β-E2can up-regulate the ER, while non-physiologic concentrations of17β-E2down-regulate the ER, and the effect of17β-E2on ER is time-dependent.2.Moreover,the synthesis and degradation of condylar cartilage matrix is closely correlated withthe level of17β-E2. Physiologic concentration of17β-E2can keep the homeostasis ofMMP-13and TIMP-1in rat condylar cartilage, to facilitate the synthesis of condylarcartilage matrix. In case of too high or too low concentration of17β-E2, theexpression of MMP-13can be significant increased, while the expression of TIMP-1and CⅡcould be largely decreased. This can induce the degradation of condylarcartilage matrix and lead to injury of joint.3.Timely replacement therapy by17β-E2supplement can effective prevent the onset and progression of TMD, as well asalleviate its symptoms.