Effects of Estrogen Level, Dietary Loading, and Aging on Types I, II, and X Collagen Expression and Structure of Rat Mandibular Condylar Cartilage

Aims: To investigate how estrogen level, dietary loading, and aging affect cartilage structure and the expression of major collagens (types I, II, and X) in rat mandibular condylar cartilage (MCC). Methods: A total of 96 outbred Sprague Dawley female rats were randomly divided into two groups by ovariectomy (OVX) at 7 weeks old. One week later, the rats in each group were further divided into three subgroups on the basis of food hardness: hard food (diet board), normal food (pellet), and soft food (powder). The rats were sacrificed at the age of 5 or 14 months. The thickness of the fibrous, proliferative, and chondroblastic layers of the mandibular condylar cartilage were measured after toluidine blue staining. Immunohistochemical analysis was performed to evaluate the expression levels of types I, II, and X collagen. A linear regression model was used to investigate the main factors affecting changes in thickness and collagen expression. Results: The expression levels of types II and X collagen were decreased by ovarian estrogen deficiency and increased by dietary loading. Increased dietary loading was the main factor affecting an increase in thickness of the cartilage layers, while aging was the main factor affecting a decrease in thickness of the fibrous layer. A significant age-related increase was found in the expression of type I collagen. There was some degree of interaction between aging and dietary loading that affected the thickness of the chondroblastic layer and the expression of type X collagen. Conclusion: The physiologic level of estrogen plays a role in MCC development by promoting the expression of types II and X collagen. Dietary loading is essential to increase the expression of types II and X collagen, as well as the thickness of cellular layers, to maintain the integrity of the MCC. Aging seems to reduce the ability of the MCC to withstand occlusal loading.

aging; collagen; dietary loading; estrogen; fibrocartilage; mandibular condylar cartilage

1. Teramoto M, Kaneko S, Shibata S, Yanagishita M, Soma K. Effect of compressive forces on extracellular matrix in rat mandibular condylar cartilage. J Bone Miner Metab 2003;21:276–286.

2. Benjamin M, Ralphs JR. Biology of fibrocartilage cells. Int Rev Cytol 2004;233:1–45.

3. Wang L, Lazebnik M, Detamore MS. Hyaline cartilage cells outperform mandibular condylar cartilage cells in a TMJ fibrocartilage tissue engineering application. Osteoarthritis Cartilage 2009;17:346–353.

4. Kuroda S, Tanimoto K, Izawa T, Fujihara S, Koolstra JH, Tanaka E. Biomechanical and biochemical characteristics of the mandibular condylar cartilage. Osteoarthritis Cartilage 2009;17:1408–1415.

5. Di Lullo GA, Sweeney SM, Korkko J, Ala-Kokko L, San Antonio JD. Mapping the ligand-binding sites and disease-associated mutations on the most abundant protein in the human, type I collagen. J Biol Chem 2002;277:4223–4231.

6. Singh M, Detamore MS. Biomechanical properties of the mandibular condylar cartilage and their relevance to the TMJ disc. J Biomech 2009;42:405–417.

7. Delatte M, Von den Hoff JW, van Rheden RE, Kuijpers-Jagtman AM. Primary and secondary cartilages of the neonatal rat: The femoral head and the mandibular condyle. Eur J Oral 2004;112:156–162.

8. Mizoguchi I, Nakamura M, Takahashi I, Kagayama M, Mitani H. An immunohistochemical study of localization of type I and type II collagens in mandibular condylar cartilage compared with tibial growth plate. Histochemistry 1990;93:593–599.

9. Wilson SL, Guilbert M, Sule-Suso J, et al. A microscopic and macroscopic study of aging collagen on its molecular structure, mechanical properties, and cellular response. FASEB J 2014;28:14–25.

10. Utreja A, Dyment NA, Yadav S, et al. Cell and matrix response of temporomandibular cartilage to mechanical loading. Osteoarthritis Cartilage 2016;24:335–344.

11. Tanaka E, Detamore MS, Mercuri LG. Degenerative disorders of the temporomandibular joint: Etiology, diagnosis, and treatment. J Dent Res 2008;87:296–307.

12. Yu J, Liang F, Huang H, Pirttiniemi P, Yu D. Effects of loading on chondrocyte hypoxia, HIF-1α and VEGF in the mandibular condylar cartilage of young rats. Orthod Craniofac Res 2018;21:41–47.

13. Okayasu I, Yamada Y, Kohno S, Yoshida N. New animal model for studying mastication in oral motor disorders. J Dent Res 2003;82:318–321.

14. Liu YD, Liao LF, Zhang HY, et al. Reducing dietary loading decreases mouse temporomandibular joint degradation induced by anterior crossbite prosthesis. Osteoarthritis Cartilage 2014;22:302–312.

15. Abubaker AO, Hebda PC, Gunsolley JN. Effects of sex hormones on protein and collagen content of the temporomandibular joint disc of the rat. J Oral Maxillofac Surg 1996;54:721–727; discussion 727–728.

16. Ribeiro-Dasilva MC, Fillingim RB, Wallet SM. Estrogen-induced monocytic response correlates with TMD pain: A case control study. J Dent Res 2017;96:285–291.

17. Nielsen RH, Christiansen C, Stolina M, Karsdal MA. Oestrogen exhibits type II collagen protective effects and attenuates collagen-induced arthritis in rats. Clin Exp Immunol 2008;152:21–27.

18. Mirahmadi F, Koolstra JH, Lobbezoo F, et al. Mechanical stiffness of TMJ condylar cartilage increases after artificial aging by ribose. Arch Oral Biol 2018;87:102–109.

19. Laaksonen KS, Nevalainen TO, Haasio K, Kasanen IH, Nieminen PA, Voipio HM. Food and water intake, growth, and adiposity of Sprague-Dawley rats with diet board for 24 months. Lab Anim 2013;47:245–256.

20. Yu J, Mursu E, Typpö M, et al. MMP-3 and MMP-8 in rat mandibular condylar cartilage associated with dietary loading, estrogen level, and aging. Arch Oral Biol 2019;97:238–244.

21. Jussila P, Knuutila J, Salmela S, et al. Association of risk factors with temporomandibular disorders in the Northern Finland Birth Cohort 1966. Acta Odontol Scand 2018;76:525–529.

22. Scrivani SJ, Keith DA, Kaban LB. Temporomandibular disor-ders. N Engl J Med 2008;359:2693–2705.

23. Landi N, Lombardi I, Manfredini D, et al. Sexual hormone serum levels and temporomandibular disorders. A preliminary study. Gynecol Endocrinol 2005;20:99–103.

24. Oestergaard S, Sondergaard BC, Hoegh-Andersen P, et al. Effects of ovariectomy and estrogen therapy on type II collagen degradation and structural integrity of articular cartilage in rats: Implications of the time of initiation. Arthritis Rheum 2006;54:2441–2451.

25. Christgau S, Tankó LB, Cloos PA, et al. Suppression of elevated cartilage turnover in postmenopausal women and in ovariectomized rats by estrogen and a selective estrogen-receptor modulator (SERM). Menopause 2004;11:508–518.

26. Shen G, Rabie AB, Zhao ZH, Kaluarachchi K. Forward deviation of the mandibular condyle enhances endochondral ossification of condylar cartilage indicated by increased expression of type X collagen. Arch Oral Biol 2006;51:315–324.

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

28. Yu S, Xing X, Jiao K, Sun L, Liu L, Wang M. Changes in the expression of aromatase, estrogen receptor alpha and beta in mandibular condylar cartilage of rats induced by disordered occlusion. BMC Musculoskelet Disord 2012;13:190.

29. Li XF, Wang SJ, Jiang LS, Dai LY. Stage specific effect of leptin on the expressions of estrogen receptor and extracellular matrix in a model of chondrocyte differentiation. Cytokine 2013;61:876–884.

30. Orajärvi M, Thesleff I, Hartikainen H, Raustia A, Pirttiniemi P. Effect of estrogen and food hardness on metabolism and turnover of condylar cartilage. J Oral Facial Pain Headache 2015;29:297–307.

31. Orajärvi M, Hirvonen O, Yu SB, et al. Effect of estrogen and altered diet hardness on the expression of estrogen receptor alpha and matrix metalloproteinase-8 in rat condylar cartilage. J Orofac Pain 2011;25:261–268.

32. Xue XT, Zhang T, Cui SJ, et al. Sexual dimorphism of estrogen-sensitized synoviocytes contributes to gender difference in temporo-mandibular joint osteoarthritis. Oral Dis 2018;24:1503–1513.

33. Ye T, Sun D, Mu T, et al. Differential effects of high-physio-logical oestrogen on the degeneration of mandibular condylar cartilage and subchondral bone. Bone 2018;111:9–22.

34. Xiao YP, Tian FM, Dai MW, Wang WY, Shao LT, Zhang L. Are estrogen-related drugs new alternatives for the management of osteoarthritis? Arthritis Res Ther 2016;18:151.

35. Enomoto A, Watahiki J, Yamaguchi T, Irie T, Tachikawa T, Maki K. Effects of mastication on mandibular growth evaluated by microcomputed tomography. Eur J Orthod 2010;32:66–70.

36. Dai M, Sui B, Xue Y, Liu X, Sun J. Cartilage repair in degen-erative osteoarthritis mediated by squid type II collagen via immunomodulating activation of M2 macrophages, inhibitingapoptosis and hypertrophy of chondrocytes. Biomaterials 2018;180:91–103.

37. Robinson JL, Cass K, Aronson R, et al. Sex differences in the estrogen-dependent regulation of temporomandibular joint remodeling in altered loading. Osteoarthritis Cartilage 2017;25:533–543.

38. Gawri R, Moir J, Ouellet J, et al. Physiological loading can restore the proteoglycan content in a model of early IVD degen-eration. PloS One 2014;9:e101233.

39. Orajärvi M, Laaksonen S, Hauru R, et al. Changes in type I and type II collagen expression in rat mandibular condylar cartilage associated with aging and dietary loading. J Oral Facial Pain Headache 2018;32:258–265.

40. Orajärvi M, Puijola E, Yu SB, et al. Effect of estrogen and dietary loading on condylar cartilage. J Orofac Pain 2012;26:328–336.

41. Polur I, Kamiya Y, Xu M, et al. Oestrogen receptor beta mediates decreased occlusal loading induced inhibition of chondrocyte maturation in female mice. Arch Oral Biol 2015;60:818–824.

42. Yadav S, Yang Y, Dutra EH, Robinson JL, Wadhwa S. Temporomandibular joint disorders in older adults. J Am Geriatr Soc 2018;66:1213–1217.

43. Ruggiero L, Zimmerman BK, Park M, et al. Roles of the fibrous superficial zone in the mechanical behavior of TMJ condylarcartilage. Ann Biomed Eng 2015;43:2652–2662.

44. Gay S, Müller PK, Lemmen C, Remberger K, Matzen K, Kühn K. Immunohistological study on collagen in cartilage-bone meta-morphosis and degenerative osteoarthrosis. Klin Wochenschr 1976;54:969–976.

45. Briggs TW, Mahroof S, David LA, Flannelly J, Pringle J, Bayliss M. Histological evaluation of chondral defects after autologous chondrocyte implantation of the knee. J Bone Joint Surg Br 2003;85:1077–1083.

46. Loeser RF, Collins JA, Diekman BO. Ageing and the pathogen-esis of osteoarthritis. Nat Rev Rheumatol 2016;12:412–420.