Effect of Estrogen and Food Hardness on Metabolism and Turnover of Condylar Cartilage

Aims: To clarify the effect of estrogen and food hardness on condylar cartilage and the cartilage-bone interface. Methods: A total of 56 rats were divided into four groups: (1) ovariectomized rats fed a normal (pressed pellet) food, (2) ovariectomized rats fed a soft (powder) food, (3) control rats fed a normal (pressed pellet) food, and (4) control rats fed a soft (powder) food. Some rats (n = 29) were sacrificed at the age of 67 days and others (n = 27) at the age of 87 days, and then 5-µm-thick sagittal paraffin sections were prepared from each temporomandibular joint (TMJ). Toluidine blue staining, in situ hybridization with type X collagen, terminal deoxynucleotidyl transferase and deoxyuridine triphosphate nick end labeling (TUNEL-assay), and tartrate-resistant acid phosphatase (TRAP) histochemistry were performed. Immunohistochemical analyses included cathepsin K, adiponectin, proliferating cell nuclear antigen (PCNA), and type X collagen staining. Analysis of variance and appropriate post-hoc tests were used in all analyses. Results: Ovariectomy and normal food consistency increased the thickness of condylar cartilage (P < .001), PCNA expression (P < .001) and type X collagen expression (P < .001). Ovariectomy decreased the number (P < .05) and size of osteoclasts (P < .01). Soft food increased the number of cartilage cells stained positively against adiponectin (P < .01). Conclusion: Decreased estrogen level and normal food hardness increase the thickness of condylar cartilage by various mechanisms.

adiponectin; estrogen; food hardness; loading; mandibular condylar cartilage; osteoclast; PCNA; proliferation; TRAP; type X collagen

1. Okeson JP. Etiology of functional disturbances in the masticatory system. In: Okeson JP (ed). Management of Temporomandibular Disorders and Occlusion. St Louis: Mosby, 2013:102–122.

2. Cairns BE. Pathophysiology of TMD pain—Basic mechanisms and their implications for pharmacotherapy. J Oral Rehabil 2010;37:391–410.

3. De Kanter RJ, Truin GJ, Burgersdijk RC, et al. Prevalence in the Dutch adult population and a meta-analysis of signs and symptoms of temporomandibular disorder. J Dent Res 1993;72: 1509–1518.

4. Kuttila M, Kuttila S, Le Bell Y, Alanen P. Association between TMD treatment need, sick leaves, and use of health care services for adults. J Orofac Pain 1997;11:242–248.

5. Carlsson GE. Epidemiology and treatment need for temporo-mandibular disorders. J Orofac Pain 1999;13:232–237.

6. 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.

7. Khosla S, Oursler MJ, Monroe DG. Estrogen and the skeleton. Trends Endocrinol Metab 2012;23:576–581.

8. May C, Harper RP, Chi T, Brendan S. Effects of estrogen on the condylar cartilage of the rat mandible in organ culture. J Oral Maxillofac Surg 1999;57:818–823.

9. 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.

10. Orajarvi 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.

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

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

13. Lee HR, Kim TH, Choi KC. Functions and physiological roles of two types of estrogen receptors, ERα and ERβ, identified byestrogen receptor knockout mouse. Lab Anim Res 2012; 28:71–76.

14. Costa AG, Cusano NE, Silva BC, Cremers S, Bilezikian JP. Cathepsin K: Its skeletal actions and role as a therapeutic target inosteoporosis. Nat Rev Rheumatol 2011;7:447–456.

15. Pickarski M, Hayami T, Zhuo Y, Duong le T. Molecular changes in articular cartilage and subchondral bone in the rat anterior cruciate ligament transection and meniscectomized models of osteoarthritis. BMC Musculoskelet Disord 2011;12:197.

16. Schmid TM, Linsenmayer TF. Immunoelectron microscopy of type X collagen: Supramolecular forms within embryonic chick cartilage. Dev Biol 1990;138:53–62.

17. 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.

18. Gomez R, Lago F, Gomez-Reino J, Dieguez C, Gualillo O. Adipokines in the skeleton: Influence on cartilage function and joint degenerative diseases. J Mol Endocrinol 2009;43:11–18.

19. de Oliveira C, de Mattos AB, Silva CB, Mota JF, Zemdegs JC. Nutritional and hormonal modulation of adiponectin and its receptors adipoR1 and adipoR2. Vitam Horm 2012;90:57–94.

20. Spangenburg EE, Wohlers LM, Valencia AP. Metabolic dysfunction under reduced estrogen levels: Looking to exercise for prevention. Exerc Sport Sci Rev 2012;40:195–203.

21. Weijs WA, Dantuma R. Electromyography and mechanics of mastication in the albino rat. J Morphol 1975;146:1–33.

22. Kiliaridis S, Thilander B, Kjellberg H, Topouzelis N, Zafiriadis A. Effect of low masticatory function on condylar growth: A morphometric study in the rat. Am J Orthod Dentofacial Orthop 1999; 116:121–125.

23. 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.

24. Yu SB, Wang MQ, Li YQ, et al. The effects of age and sex on the expression of oestrogen and its receptors in rat mandibular condylar cartilages. Arch Oral Biol 2009;54:479–485.

25. Wilkinson D, Green J. In situ hybridization and the threedimensional reconstruction of serial sections. In: Copp AJ, Cole DE (eds). Postimplantation Mammalian Embryos. London: Oxford University Press, 1990:155–171.

26. Suomalainen M, Thesleff I. Patterns of Wnt pathway activity in the mouse incisor indicate absence of Wnt/beta-catenin signaling in the epithelial stem cells. Dev Dyn 2010;239:364–372.

27. Apte SS, Seldin MF, Hayashi M, Olsen BR. Cloning of the human and mouse type X collagen genes and mapping of the mouse type X collagen gene to chromosome 10. Eur J Biochem 1992;206:217–224.

28. Tamhane AC. Multiple comparisons in model I one-way ANOVA with unequal variances. Commun Stat B-Simul 1977;9:167–178.

29. DeMuth JE: Multiple comparison tests. In: Basic Statistics and Pharmaceutical Statistical Applications. Boca Raton, Florida: Chapman and Hall/CRC, 2006:243–245.

30. Papachristou DJ, Pirttiniemi P, Kantomaa T, Papavassiliou AG, Basdra EK. JNK/ERK-AP-1/Runx2 induction “paves the way” to cartilage load-ignited chondroblastic differentiation. Histochem Cell Biol 2005;124:215–223.

31. Rabie AB, She TT, Hägg U. Functional appliance therapy accelerates and enhances condylar growth. Am J Orthod Dentofacial Orthop 2003;123:40–48.

32. Luder HU. Macroscopic and microscopic joint morphology, relationship to metabolic activity. In: McNamara JA (ed). Postnatal Development, Aging, and Degeneration of the Temporomandibular Joint in Humans, Monkeys, and Rats (Vol 32). AnnArbor: Center for Human Growth and Development, University of Michigan, 1996:72–109.

33. Yanagishita M. Function of proteoglycans in the extracellular matrix. Acta Pathol Jpn 1993;43:283–293.

34. Kuroda S, Tanimoto K, Izawa T, et al. Biomechanical and biochemical characteristics of the mandibular condylar cartilage. Osteoarthritis Cartilage 2009;17:1408–1415.

35. Kinumatsu T, Shibukawa Y, Yasuda T, et al. TMJ development and growth require primary cilia function. J Dent Res 2011; 90:988–994.

36. Shevde NK, Bendixen AC, Dienger KM, Pike JW. Estrogens suppress RANK ligand-induced osteoclast differentiation via a stromal cell independent mechanism involving c-Jun repression. Proc Natl Acad Sci U S A 2000;97:7829–7834.

37. Hofbauer LC, Khosla S, Dunstan CR, et al. Estrogen stimulates gene expression and protein production of osteoprotegerin in human osteoblastic cells. Endocrinology 1999;140: 4367–4370.

38. Yamashiro T, Takano-Yamamoto T. Differential responses of mandibular condyle and femur to oestrogen deficiency in young rats. Arch Oral Biol 1998;43:191–195.

39. Pirttiniemi P, Kantomaa T, Salo L, Tuominen M. Effect of reduced articular function on deposition of type I and type II collagens in the mandibular condylar cartilage of the rat. Arch Oral Biol 1996;41:127–131.

40. Karaplis AC, Luz A, Glowacki J, et al. Lethal skeletal dysplasia from targeted disruption of the parathyroid hormone-related peptide gene. Genes Dev 1994;8:277–289.

41. Chung UI, Schipani E, McMahon AP, Kronenberg HM. Indian hedgehog couples chondrogenesis to osteogenesis in endochondral bone development. J Clin Invest 2001;107:295–304.

42. Kronenberg HM. Developmental regulation of the growth plate. Nature 2003;423:332–336.

43. Suda N, Shibata S, Yamazaki K, et al. Parathyroid hormone-related protein regulates proliferation of condylar hypertrophic chondrocytes. J Bone Miner Res 1999;14:1838–1847.

44. Santaniemi M, Kesäniemi YA, Ukkola O. Low plasma adiponectin concentration is an indicator of the metabolic syndrome. Eur J Endocrinol 2006;155:745–750.

45. Francin PJ, Guillaume C, Humbert AC, et al. Association between the chondrocyte phenotype and the expression of adipokines and their receptors: Evidence for a role of leptin but not adiponectin in the expression of cartilage-specific markers. J Cell Physiol 2011;226:2790–2797.

46. Ukkola O, Santaniemi M. Adiponectin: A link between excess adiposity and associated comorbidities? J Mol Med (Berl) 2002; 80:696–702.

47. Schäffler A, Ehling A, Neumann E, et al. Adipocytokines in sy-novial fluid. JAMA 2003;290:1709–1710.

48. Dijkgraaf LC, de Bont LG, Boering G, Liem RS. The structure, biochemistry, and metabolism of osteoarthritic cartilage: A review of the literature. J Oral Maxillofac Surg 1995;53: 1182–1192.

49. Jiao K, Wang MQ, Niu LN, et al. Death and proliferation of chondrocytes in the degraded mandibular condylar cartilage ofrats induced by experimentally created disordered occlusion. Apoptosis 2009;14:22–30.