[The effect of estrogen and progestin on the expression of matrix metalloproteinases, tissue inhibitor of metalloproteinase and interleukin-1beta mRNA in synovia of OA rabbit model].
OBJECTIVE
To observe the effect of different dose of estrogen or estrogen plus progestin on the mRNA expression of MMP-1, MMP-3, TIMP-1 and IL-1beta in synovia of female New Zealand White rabbit OA model.


METHODS
Sixty-five female New Zealand White rabbits (3 kg +/-, 6 months old) were used in this study. Right knees of all the rabbits were immobilized for 5 weeks to get OA model. Then 5 rabbits were killed by overdose of anesthesia to guarantee the model. Sixty OA rabbits were randomly divided into 6 groups (A, B, C, D, E, F) with 10 each. Group A approximately E were ovariectomized and group F were sham ovariectomized. The rabbits were feed by estradiol valerate (E(2)V) everyday as follows. Group A: E(2)V 1.8 mg/d, group B: E(2)V 3.6 mg/d, group C: E(2)V 7.2 mg/d, group D: E(2)V 3.6 mg/d + MPA 3.6 mg/d, group E was the untreated control group, group F was the untreated sham control group. Five rabbits of each group were killed respectively in 8 and 16 weeks and synovia of the right knee were obtained on all knees. Reverse transcription- polymerase chain reaction were used to detect the mRNA expression of MMP-1, MMP-3, TIMP-1 and IL-1beta in the OA synovia to determine the effect of estrogen and progestin.


RESULTS
RT-PCR shows an increase expression of mRNA of MMP-1, MMP-3 and IL-1beta in OA synovia tissue in ovariectomized rabbits. Estrogen supplement could decrease the expression, an enhancement effect could be observed with progestin. Low dose estrogen could decrease the ratio of MMP-1/TIMP-1 and MMP-3/TIMP-1, which could even be decreased by progestin. High dose estrogen could slightly increase the ratio, but still lower than the untreatment control group.


CONCLUSIONS
Our study suggests that certain dose estrogen and perhaps appropriate estrogen and progestin ratio are much important to the normal effect of articular cartilage. Estrogen deficiency or much high estrogen level could both show a damage effect on articular cartilage.
Song
Yi-jun
YJ
Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medecal Science, Beijing 100730, China.
Wu
Zhi-hong
ZH
Lin
Shou-qing
SQ
Weng
Xi-sheng
XS
Qiu
Gui-xing
GX
D000818:Animals; D004195:Disease Models, Animal; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D007375:Interleukin-1 / Q000235:genetics*; D020781:Matrix Metalloproteinase 1 / Q000235:genetics*; D019278:Matrix Metalloproteinase 3 / Q000235:genetics*; D010003:Osteoarthritis / Q000378:metabolism*; D011372:Progestins / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis*; D011817:Rabbits; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics*
D004967:Estrogens; D007375:Interleukin-1; D011372:Progestins; D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D019278:Matrix Metalloproteinase 3; D020781:Matrix Metalloproteinase 1