Abstract
Objectives
We have previously reported that relaxin (Rln) expression from the ovary is upregulated by orthodontic tooth movement. This study was performed to test the hypothesis that Rln family peptides (Rxfps), the G-protein-coupled Rln receptor, is induced in periodontal ligament (PDL) cells to modulate the molecules involved in periodontal tissue remodeling while applying biophysical force.
Materials and methods
Rats were implanted with orthodontic appliances to investigate changes to Rxfps in vivo. An in vitro biophysical force analysis was performed to measure the level of Rxfp 1 messenger RNA (mRNA) in primary human PDL cells.
Results
The levels of Rxfp 2 transcription and translation increased in a time-dependent manner during tooth movement. Rxfp 2 was localized in the PDL by immunofluorescence. In vitro analyses revealed that the level of Rxfp 1 mRNA in PDL cells increased significantly with both compression and tension force. The levels of matrix metalloproteinase (MMP)-1, MMP-2, interleukin-6, and vascular endothelial growth factor mRNA, which are important for periodontal tissue remodeling, also changed under force application and Rln treatment.
Conclusions
PDL cells responded to Rln to modulate effector molecules for periodontal tissue remodeling by upregulating Rxfps expression under a biophysical force.
Clinical relevance
Rln and Rxfps may serve as a PDL turnover molecule complex to control orthodontic tooth movement.
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References
Nakagawa M, Kukita T, Nakasima A, Kurisu K (1994) Expression of the type I collagen gene in rat periodontal ligament during tooth movement as revealed by in situ hybridization. Arch Oral Biol 39(4):289–294
Krishnan V, Davidovitch Z (2006) Cellular, molecular, and tissue-level reactions to orthodontic force. Am J Orthod Dentofacial Orthop 129(4):469 e1–32
Bathgate RA, Halls ML, van der Westhuizen ET, Callander GE, Kocan M et al (2013) Relaxin family peptides and their receptors. Physiol Rev 93(1):405–480
Ferlin A, Pepe A, Facciolli A, Gianesello L, Foresta C (2010) Relaxin stimulates osteoclast differentiation and activation. Bone 46(2):504–513
Kong RC, Shilling PJ, Lobb DK, Gooley PR, Bathgate RA (2010) Membrane receptors: structure and function of the relaxin family peptide receptors. Mol Cell Endocrinol 320(1–2):1–15
Lopatiene K, Dumbravaite A (2008) Risk factors of root resorption after orthodontic treatment. Stomatologija 10(3):89–95
Ngom PI, Benoist HM, Soulier-Peigue D, Niang A (2010) Reciprocal relationships between orthodontics and periodontics: relevance of a synergistic action. Orthod Fr 81(1):41–58
Soma S, Matsumoto S, Higuchi Y, Takano-Yamamoto T, Yamashita K, Kurisu K et al (2000) Local and chronic application of PTH accelerates tooth movement in rats. J Dent Res 79(9):1717–1724
Poosti M, Basafa M, Eslami N (2009) Progesterone effects on experimental tooth movement in rabbits. J Calif Dent Assoc 37(7):483–486
Henneman S, Bildt MM, deGroot J, Kuijpers-Jagtman AM, Von den Hoff JW (2008) Relaxin stimulates MMP-2 and α-smooth actin expression by human periodontal ligament cells. Arch Oral Biol 53:161–167
Takano M, Yamaguchi M, Nakajima R, Fujit S, Kojima T, Kasai K (2009) Effects of relaxin on collagen type I released by stretched human periodontal ligament cells. Orthod Craniofac Res 12:282–288
Hirate Y, Yamaguchi M, Kasai K (2012) Effects of relaxin on relapse and periodontal tissue remodeling after experimental tooth movement in rats. Connect Tissue Res 53(3):207–219
Liu ZJ, King GJ, Gu GM, Shin JY, Stewart DR (2005) Does human relaxin accelerate orthodontic tooth movement in rats? Ann N Y Acad Sci 1041:388–394
Madan MS, Liu ZJ, Gu GM, King GJ (2007) Effects of human relaxin on orthodontic tooth movement and periodontal ligaments in rats. Am J Orthod Dentofacial Orthop 131(1):8.e1–10
McGorray SP, Dolce C, Kramer S, Stewart D, Wheeler TT (2012) A randomized, placebo-controlled clinical trial on the effects of recombinant human relaxin on tooth movement and short-term stability. Am J Orthod Dentofacial Orthop 141(2):196–203
Yang SY, Ko HM, Kang JH, Moon YH, Yoo HI, Jung NR et al (2011) Relaxin is up-regulated in the rat ovary by orthodontic tooth movement. Eur J Oral Sci 119(2):115–120
Ren Y, Maltha JC, Kuijpers-Jagtman AM (2004) The rat as a model for orthodontic tooth movement—a critical review and a proposed solution. Eur J Orthod 26(5):483–490
Viecilli RF, Katona TR, Chen J, Hartsfield JK Jr, Roberts WE (2008) Three-dimensional mechanical environment of orthodontic tooth movement and root resorption. Am J Orthod Dentofacial Orthop 133(6):791.e11–26
Fill TS, Carey JP, Toogood RW, Major PW (2011) Experimentally determined mechanical properties and models for the periodontal ligament: critical review of current literature. J Dent Biomech 2011:1–6
Fill TS, Toogood RW, Major PW, Carey JP (2012) Analytically determined mechanical properties of, and models for the periodontal ligament: critical review of literature. J Biomech 45(1):9–16
Natali AN, Pavan PG, Scarpa C (2004) Numerical analysis of tooth mobility: formulation of a non-linear constitutive law for the periodontal ligament. Dent Mater 20(7):623–629
Gosset M, Berenbaum F, Levy A, Pigenet A, Thirion S, Saffar JL, Jacques C (2006) Prostaglandin E2 synthesis in cartilage explants under compression: mPGES-1 is a mechanosensitive gene. Arthritis Res Ther 8(4):R135
Li Y, Li M, Tan L, Huang S, Zhao L, Tang T, Liu J, Zhao Z (2013) Analysis of time-course gene expression profiles of a periodontal ligament tissue model under compression. Arch Oral Biol 58:511–522
Yousefian J, Firouzian F, Shanfeld J, Ngan P, Lanese R, Davidovitch Z (1995) A new experimental model for studying the response of periodontal ligament cells to hydrostatic pressure. Am J Orthod Dentofacial Orthop 108(4):402–409
Schwarz AM (1932) Tissue changes incidental to orthodontic tooth movement. Int J Orthod 18:331–340
Brown TD (2000) Techniques for mechanical stimulation of cells in vitro: a review. J Biomech 33(1):3–14
Wang Y, Cai LQ, Nugraha B, Gao Y, Liang LH (2013) Current hydrogel solutions for repairing and regeneration of complex tissues. Curr Med Chem [Epub ahead of print]
Hsu SY, Nakabayashi K, Nishi S, Kumagai J, Kudo M, Sherwood OD et al (2002) Activation of orphan receptors by the hormone relaxin. Science 295(5555):671–674
Halls ML, Bathgate RA, Summers RJ (2006) Relaxin family peptide receptors RXFP1 and RXFP2 modulate cAMP signaling by distinct mechanisms. Mol Pharmacol 70(1):214–226
Bryant-Greenwood GD, Yamamoto SY, Sadowsky DW, Gravett MG, Novy MJ (2009) Relaxin stimulates interleukin-6 and interleukin-8 secretion from the extraplacental chorionic cytotrophoblast. Placenta 30(7):599–606
Horton JS, Yamamoto SY, Bryant-Greenwood GD (2011) Relaxin modulates proinflammatory cytokine secretion from human decidual macrophages. Biol Reprod 85(4):788–797
Abdel Meguid MH, Hamad YH, Swilam RS, Barakat MS (2013) Relation of interleukin-6 in rheumatoid arthritis patients to systemic bone loss and structural bone damage. Rheumatol Int 33(3):697–703
Goldman WH (2012) Mechanotransduction in cells. Cell Biol Int 36:567–570
Ferlin A, Perilli L, Gianesello L, Taglialavoro G, Foresta C (2011) Profiling insulin like factor 3 (INSL3) signaling in human osteoblasts. PLoS One 6(12):e29733
Acknowledgments
This work was supported by the National Research Foundation of Korea Grant funded by the Korean Government (2009-0069147) and the National Research Foundation of Korea (NRF) grant, funded by the Korea government (MSIP) (2011-0030121).
Conflict of interest
The authors declare no potential conflicts of interest with respect to the authorship and/or publication of this article.
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J.W. Kim contributed to this work equally to the first author.
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Yang, S.Y., Kim, J.W., Lee, S.Y. et al. Upregulation of relaxin receptors in the PDL by biophysical force. Clin Oral Invest 19, 657–665 (2015). https://doi.org/10.1007/s00784-014-1276-4
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DOI: https://doi.org/10.1007/s00784-014-1276-4