Effect of Estrogen and Altered Diet Hardness on the Expression of Estrogen Receptor Alpha and Matrix Metalloproteinase-8 in Rat Condylar Cartilage

Aims: To examine the effect of decreased estrogen level and altered diet hardness on condylar cartilage morphology of the rat temporomandibular joint (TMJ) and on the expression of condylar cartilage estrogen receptor alpha (ERα) and matrix metalloproteinase-8 (MMP-8). Methods: A total of 36 female rats was divided into four groups: ovariectomized rats fed a normal diet, non-ovariectomized controls fed a normal diet, ovariectomized rats fed a soft diet, and non-ovariectomized controls fed a soft diet. Ovariectomy was performed at the age of 60 days. Seven days after the operation, the rats were sacrificed. Repeated measures ANOVA and Duncan’s multiple comparison tests were used for statistical analysis. Results: The ovariectomized rats had thicker cartilage layers than the controls, both in the normal diet and soft diet groups. The thinnest cartilage layers were found in the control rats fed with the soft diet. The thickness of the chondroblastic layer was significantly higher (P < .001) in the normal-diet rats than in the soft-diet rats in both ovariectomized and non-ovariectomized groups. The thickness of the proliferative layer was significantly higher (P < .001) in the ovariectomized soft-diet rats than in the soft-diet control rats. The proportional amount of ERα was statistically significantly higher (P < .001) in the condylar cartilage of the ovariectomized rats than in the non-ovariect-omized control rats both in the normal- and soft-diet groups. The proportional amount of ERα was statistically significantly higher (P < .001) in the ovariectomized normal-diet rats than in the ovariec-tomized soft-diet rats. The proportional number of MMP-8–positive cells was statistically significantly higher (P < .001) in the condylar cartilage of ovariectomized rats fed the soft diet than in non-ovariectomized control rats fed the soft diet. Control rats fed with the normal diet had a higher proportional amount of MMP-8 positive cells than control rats fed with the soft diet (P < .05). Conclusion: The rat TMJ condylar cartilage is sensitive to changes in estrogen levels and altered diet hardness.

ERα;estrogen;joint loading;mandibular condylar cartilage;MMP-8

1.Okeson JP. Management of Temporomandibular Disorders and Occlusion, ed 6. St Louis: Elsevier Mosby, 2008.

2.Rutkiewicz T, Könönen M, Suominen-Taipale L, Nordblad A, Alanen P. Occurrence of clinical signs of temporomandibular disorders in adult Finns. J Orofac Pain 2006;20:208–217.

3.Warren MP, Fried JL. Temporomandibular disorders and hormones in women. Cells Tissues Organs 2001;169:187–192.

4.Kang SC, Lee DG, Choi JH, Kim ST, Kim YK, Ahn HJ. Association between estrogen receptor polymorphism and pain susceptibility in female temporomandibular joint osteoarthritis patients. J Oral Maxillofac Surg 2007;36:391–394.

5.Simpson ER, Clyne C, Rubin G, et al. Aromatase: A brief overview. Annu Rev Physiol 2002;64:93–127.

6.Yu SBB, Wang MQ, Zhao W, Cao HT, Liu YL. The effects of age and sex on the expression of aromatase in the rat temporomandibular joint. J Orofac Pain 2006;20:165 –156.

7.Talwar RM, Wong BS, Svoboda K, Harper RP. Effect of estrogen on chondrocyte proliferation and collagen synthesis in skeletally mature articular cartilage. J Oral Maxillofac Surg 2006;64:600–609.

8.Yamada K, Nozawa-Inoue K, Kawano Y, et al. Expression of estrogen receptor alpha (ER alpha) in the rat temporomandibular joint. Anat Rec A Discov Mol Cell Evol Biol 2003;274:934–941.

9.Tiilikainen P, Raustia A, Pirttiniemi P. Effect of diet hardness on mandibular condylar cartilage metabolism. J Orofac Pain 2011;25:68–74.

10.McNeill C. Science and Practice of Occlusion. Chicago: Quintessence, 1997:235–258.

11.Palosaari H, Wahlgren J, Larmas M, et al. The expression of MMP-8 in human odontoblasts and dental pulp cells is down-regulated by TGF-beta1. J Dent Res 2000;79:77–84.

12.Cole AA, Chubinskaya S, Schumacher B, et al. Chondrocyte matrix metalloproteinase-8. Human articular chondrocytes express neutrophil collagenase. J Biol Chem 1996;271:11023–11026.

13.Tiilikainen P, Pirttiniemi P, Kainulainen T, Pernu H, Raus-tia A. MMP-3 and -8 expression is found in the condylar surface of temporomandibular joints with internal derangement. J Oral Pathol Med 2005;34:39–45.

14.Yun K-I, Chang-Hoon C., Cheol-Won L. Effect of Estrogen on the expression of cytokines of the temporomandibular joint cartilage cells of the mouse. J Oral Maxillofac Surg 2008;66:882–887.

15.Pirttiniemi P, Kantomaa T, Sorsa T. Effect of decreased load-ing on the metabolic activity of the mandibular condylar cartilage in the rat. Eur J Orthod 2004;26:1–5.

16.Hinton RJ. Alterations in rat condylar cartilage following discectomy. J Dent Res 1992;71:1292–1297.

17.Hishikawa Y, Damavandi E, Izumi S, Koji T. Molecular histochemical analysis of estrogen receptor alpha and beta expressions in the mouse ovary: In situ hybridization and southwestern histochemistry. Med Electron Microsc 2003;36:67–73.

18.Yao X, Chen H, Ohtake N, Shoumura S. Morphological alterations in the growth plate cartilage of ovariectomized mice. Med Mol Morphol 2006;39:193–197.

19.Ornoy A, Giron S, Aner R, Goldstein M, Boyan BD, Schwartz Z. Gender dependent effects of testosterone and 17 beta-estradiol on bone growth and modelling in young mice. Bone Miner 1994;24:43–58.

20.Yao X, Chen H, Ohtake N, Shoumura S. Morphological alterations in the growth plate cartilage of ovariectomized mice. Med Mol Morphol 2006;39:193–197.

21.Yasuoka T, Nakashima M, Okuda T, Tatematsu N. Effect of estrogen replacement on temporomandibular joint re-modeling in ovariectomized rats. J Oral Maxillofac Surg 2000;58:189–196.

22.Asarian L, Geary N. Cyclic estradiol treatment normalizes body weight and restores physiological patterns of sponta-neous feeding and sexual receptivity in ovariectomized rats. Horm Behav 2002;42:461–471.

23.Yu Z, Geary N, Corwin RL. Ovarian hormones inhibit fat intake under binge-type conditions in ovariectomized rats. Physiol Behav 2008;95:501–507.

24.Bai Y, Luo S. An experimental study on the changes of estro-gen receptor in the condylar cartilages with DCC method in rats after functional mandibular protrusion. Chinese J Stomatol 1998;33:372–374.

25.Birkedal-Hansen H. Proteolytic remodeling of extracellular matrix. Curr Opin Cell Biol 1995;7:728–735.

26.Herman MP, Sukhova GK, Libby P, et al. Expression of neu-trophil collagenase (matrix metalloproteinase-8) in human atheroma: A novel collagenolytic pathway suggested by transcriptional profiling. Circulation 2001;104:1899–1904.

27.Egeblad M, Werb Z. New functions for the matrix met-alloproteinases in cancer progression. Nat Rev Cancer 2002;2:161–174.

28.Haskin CL, Milam SB, Cameron IL. Pathogenesis of degenerative joint disease in the human temporomandibular joint. Crit Rev Oral Biol Med 1995;6:248–277.

29.Wang J, Chao Y, Wan Q, Zhu Z. The possible role of estrogen in the incidence of temporomandibular disorders. Med Hypotheses 2008;71:564–567.

30.Stremme S, Duerr S, Bau B, Schmid E, Aigner T. MMP-8 is only a minor gene product of human adult articular chondrocytes of the knee. Clin Exp Rheumatol 2003;21:205–209.

31.Golub LM, Ramamurthy NS, Llavaneras A, et al. A chemically modified nonantimicrobial tetracycline (CMT-8) inhibits gingival matrix metalloproteinases, periodontal breakdown, and extra-oral bone loss in ovariectomized rats. Ann NY Acad Sci 1999;878:290–310.

32.Li J, Liao EY, Dai RC, Wei QY, Luo XH. Effects of 17 betaestradiol on the expression of interstitial collagenases-8 and - 13 (MMP-8 and MMP-13) and tissue inhibitor of metal-loproteinase-1 (TIMP-1) in ovariectomized rat osteoblastic cells. J Mol Histol 2004;35:723–731.

33.Odman A, Mavropoulos A, Kiliaridis S. Do masticatory functional changes influence the mandibular morphology in adult rats. Arch Oral Biol 2008;53:1149–1154.