Abstract
Periostin is essential for periodontal tissue integrity and homeostasis and also associated with periodontitis and periodontitis healing. This study aims to investigate the temporal and spatial expression of Periostin and Wnt5a/CaMKII in periodontitis and how the Wnt5a regulates Periostin through CaMKII signaling pathway in PDLCs in inflammatory environment. The experimental periodontitis mice were adopted to clarify the temporal and spatial expression of Wnt5a, CaMKII and Periostin during early periodontitis. And the Wnt5a, CaMKII and Periostin expression pattern and regulation mechanism in PDLCs were clarified in Porphyromonas gingivalis Lipopolysaccharide (P.g. LPS) induced inflammatory condition. Along with the periodontitis development, Wnt5a, CaMKII and Periostin significantly increased in periodontal ligament and partially increased in gingiva during 0 to 6 day (P < 0.05). They were involved in early periodontitis homeostasis especially in periodontal ligament tissue. Meanwhile, Wnt5a, CaMKII and Periostin were significantly decreased at 12 h (P < 0.05) and increased at 48 h (P < 0.05) in PDLCs after induced by P.g. LPS. Besides, Wnt5a significantly enhanced total CaMKII protein (P < 0.05), pCaMKII (P < 0.001) and Periostin (P < 0.001), and this could be blocked by CaMKII inhibitor KN93 (P < 0.05). In conclusions, in early periodontitis, Wnt5a/CaMKII and Periostin should be involved in maintaining periodontal homeostasis and Wnt5a could up-regulate Periostin via CaMKII pathway in inflammation, which would provide new clues for us to understand the pathogenesis of periodontitis and develop better therapeutic strategies.
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References
Abe T, Hajishengallis G (2013) Optimization of the ligature-induced periodontitis model in mice. J Immunol Methods 394:49–54. https://doi.org/10.1016/j.jim.2013.05.002
Ailiang Z, Shuanghua H, Xiaoliang S, Lianghua D, Xinnan B, Neng W (2014) Wnt5a promotes migration of human osteosarcoma cells by triggering a phosphatidylinositol-3 kinase/Akt signals. Cancer Cell Int 14:15. https://doi.org/10.1186/1475-2867-14-15
Aral CA, Koseoglu S, Saglam M, Pekbagriyanik T, Savran L (2016) Gingival crevicular fluid and salivary periostin levels in non-smoker subjects with chronic and aggressive periodontitis : periostin levels in chronic and aggressive periodontitis. Inflammation 39:986–993. https://doi.org/10.1007/s10753-016-0328-0
Arslan R, Karsiyaka Hendek M, Kisa U, Olgun E (2020) The effect of non-surgical periodontal treatment on gingival crevicular fluid periostin levels in patients with gingivitis and periodontitis. Oral Dis 00:1–9. https://doi.org/10.1111/odi.13664
Balli U, Keles ZP, Avci B, Guler S, Cetinkaya BO, Keles GC (2015) Assessment of periostin levels in serum and gingival crevicular fluid of patients with periodontal disease. J Periodontal Res 50:707–713. https://doi.org/10.1111/jre.12254
Bartold PM, Dyke TE (2000) Periodontitis: a host-mediated disruption of microbial homeostasis. Unlearning learned concepts. Periodontology 62:203–217. https://doi.org/10.1111/j.1600-0757.2012.00450.x
Esfahrood ZR, Vardian ST, Yadegari Z, Adhim M, Saravi NSV (2018) Periostin levels in saliva of patients with chronic periodontitis. Adv Healthcare Mater 22:25–27. https://doi.org/10.1002/adhm.20180075010.4103/jisp.jisp_239_17
Haftcheshmeh SM, Mohammadi A, Soltani A, Momtazi-Borojeni AA (2018) Evaluation of STAT1 and Wnt5a gene expression in gingival tissues of patients with periodontal disease. J Cell Biochem 120:1827–1834. https://doi.org/10.1002/jcb.27487
Haoning T, Yu X, Yang Y, Ruixin W, Lina G, Faming C (2016) Stem cells derived from “inflamed” and healthy periodontal ligament tissues and their sheet functionalities: a patient-matched comparison. J Clin Periodontol 43:72–84. https://doi.org/10.1111/jcpe.12501
Hasegawa D, Wada N, Maeda H, Yoshida S, Mitarai H, Tomokiyo A, Monnouchi S, Hamano S, Yuda A, Akamine A (2015) Wnt5a induces collagen production by human periodontal ligament cells through TGFbeta1-mediated upregulation of periostin expression. J Cell Physiol 230:2647–2660. https://doi.org/10.1002/jcp.24950
Hasegawa D, Wada N, Yoshida S, Mitarai H, Arima M, Tomokiyo A, Hamano S, Sugii H, Maeda H (2018) Wnt5a suppresses osteoblastic differentiation of human periodontal ligament stem cell-like cells via Ror2/JNK signaling. J Cell Physiol 233:1752–1762. https://doi.org/10.1002/jcp.26086
Hiromi N, Nawarat W-a, Toshiyuki N, Yasuhiro Y, Reiko Y, Yukiko B, Hiroaki K, Janjura K, Doosadee H, Waranuch P, A BJ, Yuichi I (2012) Modulation of Wnt5a expression by periodontopathic bacteria. PLoS ONE 7:e34434. https://doi.org/10.1371/journal.pone.0034434
JungEun K, Yong KS, Yeon LS, Elliott K, YoonJae S (2014) Role of Ca2+/calmodulin-dependent kinase II-IRAK1 interaction in LMP1-induced NF-κB activation. Mol Cell Biol 34:325–334. https://doi.org/10.1128/mcb.00912-13
Kumaresan D, Balasundaram A, Naik VK, Appukuttan DP (2016) Gingival crevicular fluid periostin levels in chronic periodontitis patients following nonsurgical periodontal treatment with low-level laser therapy. Eur J Dent 10:546–550. https://doi.org/10.4103/1305-7456.195179
Lusai X, Mo C, Ling H, Bin C, Yu D, Xinchun Z, Chen Z, Chenglin W, Mao JJ, Junqi L (2014) Wnt5a regulates dental follicle stem/progenitor cells of the periodontium. Stem Cell Res Ther 5:135. https://doi.org/10.1186/scrt525
Mamalis A, Markopoulou C, Lagou A, Vrotsos I (2011) Oestrogen regulates proliferation, osteoblastic differentiation, collagen synthesis and periostin gene expression in human periodontal ligament cells through oestrogen receptor beta. Arch Oral Biol 56:446–455. https://doi.org/10.1016/j.archoralbio.2010.11.001
Nagihan B, Toshiharu A, Belibasakis GN, George H (2019) TREM-1 Is Upregulated in Experimental Periodontitis, and Its Blockade Inhibits IL-17A and RANKL Expression and Suppresses Bone loss. J Clinl Med. https://doi.org/10.3390/jcm8101579
Padial-Molina M, Volk SL, Rios HF (2014) Periostin increases migration and proliferation of human periodontal ligament fibroblasts challenged by tumor necrosis factor -alpha and Porphyromonas gingivalis lipopolysaccharides. J Periodontal Res 49:405–414. https://doi.org/10.1111/jre.12120
Padial-Molina M, Volk SL, Rios HF (2015) Preliminary insight into the periostin leverage during periodontal tissue healing. J Clin Periodontol 42:764–772. https://doi.org/10.1111/jcpe.12432
Padial-Molina M, Volk SL, Rodriguez JC, Marchesan JT, Galindo-Moreno P, Rios HF (2013) Tumor necrosis factor-alpha and Porphyromonas gingivalis lipopolysaccharides decrease periostin in human periodontal ligament fibroblasts. J Periodontol 84:694–703. https://doi.org/10.1902/jop.2012.120078
Padial-Molina M, Volk SL, Taut AD, Giannobile WV, Rios HF (2012) Periostin is down-regulated during periodontal inflammation. J Dent Res 91:1078–1084. https://doi.org/10.1177/0022034512459655
Papapanou PN, Mariano S, Nurcan B, Thomas D, Magda F, Fine DH, Fleming TF, Raul G, Giannobile WV, Filippo G, Henry G, David H, Richard TK, Moritz K, Denis FK, Keith LK, Thomas K, Kenneth SK, Purnima SK, Bruno GL, Eli M, Huanxin M, Andrea M, Ian N, Steven O, Gregory JS, Ricardo T, Maurizio ST (2018) Periodontitis: consensus report of workgroup 2 of the 2017 world workshop on the classification of periodontal and peri-implant diseases and conditions. J Clin Periodontol 45(Supl20):S160–S170
Park JH, Lee NK, Lee SY (2017) Current understanding of rank signaling in osteoclast differentiation and maturation. Mol Cells 40:706–713. https://doi.org/10.14348/molcells.2017.0225
Pashirzad M, Shafiee M, Rahmani F, Behnam-Rassouli R, Hoseinkhani F, Ryzhikov M, Moradi Binabaj M, Parizadeh MR, Avan A, Hassanian SM (2017) Role of Wnt5a in the pathogenesis of inflammatory diseases. J Cell Physiol 232:1611–1616. https://doi.org/10.1002/jcp.25687
Peng Z, Dajun Q, Jianye P, Xiaoju X, Yu L, Bin K, He H (2017) Role of CaMKII in free fatty acid/hyperlipidemia-induced cardiac remodeling both in vitro and in vivo. J Mol Cell Cardiol 109:1–16. https://doi.org/10.1016/j.yjmcc.2017.06.010
Pereira C, Schaer DJ, Bachli EB, Kurrer MO, Schoedon G (2008) Wnt5A/CaMKII signaling contributes to the inflammatory response of macrophages and is a target for the antiinflammatory action of activated protein C and interleukin-10. Arterioscler Thromb Vasc Biol 28:504–510. https://doi.org/10.1161/atvbaha.107.157438
Radhika BN, Appukuttan DP, Prakash PSG, Subramanian S, Victor DJ, Balasundaram A (2019) Estimation of periostin and tumour necrosis factor-alpha in type II Diabetics with Chronic Periodontitis: a case-control study. J Indian Soc Periodontol 23:106–112. https://doi.org/10.4103/jisp.jisp_397_18
Rios HF, Ma D, Xie Y, Giannobile WV, Bonewald LF, Conway SJ, Feng JQ (2008) Periostin is essential for the integrity and function of the periodontal ligament during occlusal loading in mice. J Periodontol 79:1480–1490. https://doi.org/10.1902/jop.2008.070624
Romanos GE, Asnani KP, Hingorani D, Deshmukh VL (2014) PERIOSTIN: role in formation and maintenance of dental tissues. Int J Endocrinol 229:1–5. https://doi.org/10.1155/2014/18030410.1002/jcp.24407
Sara M, Maddalena I, Rosaria RM, Giovanni G, Gaetano DS, Eleonora L, Lucio P, Gianfranco F, Guido R, Mario V (2009) Insulin stimulates fibroblast proliferation through calcium-calmodulin-dependent kinase II. Cell cycle (Georgetown, Tex) 8:2024–2030. https://doi.org/10.4161/cc.8.13.8813
Seales EC, Micoli KJ, McDonald JM (2006) Calmodulin is a critical regulator of osteoclastic differentiation, function, and survival. J Cell Biochem 97:45–55. https://doi.org/10.1002/jcb.20659
Seubbuk S, Sritanaudomchai H, Kasetsuwan J, Surarit R (2017) High glucose promotes the osteogenic differentiation capability of human periodontal ligament fibroblasts. Mol Med Rep 15:2788–2794. https://doi.org/10.3892/mmr.2017.6333
Shujuan G, Jian K, Baohui J, Weihua G, Yi D, Yafei W, Weidong T (2017) Periodontal-derived mesenchymal cell sheets promote periodontal regeneration in inflammatory microenvironment. Tissue Eng Part A 23:585–596. https://doi.org/10.1089/ten.TEA.2016.0334
Singh MV, Anderson ME (2011) Is CaMKII a link between inflammation and hypertrophy in heart? Sci Signal 89:537–543. https://doi.org/10.1126/scisignal.aar372110.1007/s00109-011-0727-5
Sophia K 2nd, Suresh S, SudhakarSr U, Abdul Cader Jr S, Vardhini VM, Arunachalam LT, Jean SC (2020) Comparative evaluation of serum and gingival crevicular fluid periostin levels in periodontal health and disease: a biochemical study. Cureus 12:e7218. https://doi.org/10.7759/cureus.7218
Sun HJ, Seung-Youp L, Jeong-Chae L (2010) Wnt/beta-catenin signaling enhances osteoblastogenic differentiation from human periodontal ligament fibroblasts. Mol Cells 30:449–454. https://doi.org/10.1007/s10059-010-0139-3
Takeshita S, Kikuno R, Tezuka K, Amann E (1993) Osteoblast-specific factor 2: cloning of a putative bone adhesion protein with homology with the insect protein fasciclin I. Biochem J 294(Pt 1):271–278. https://doi.org/10.1042/bj2940271
Tang Y, Liu L, Wang P, Chen D, Wu Z, Tang C (2017) Periostin promotes migration and osteogenic differentiation of human periodontal ligament mesenchymal stem cells via the Jun amino-terminal kinases (JNK) pathway under inflammatory conditions. Cell Prolif 50(e12369):1–11. https://doi.org/10.1111/cpr.12369
Wei X, Liu Q, Guo S, Wu Y (2021) Role of Wnt5a in periodontal tissue development, maintenance, and periodontitis: Implications for periodontal regeneration (Review). Mol Med Rep 23:167. https://doi.org/10.3892/mmr.2020.11806
Wei Z, Dongqin C, Feng Q, Jing W, Wenyan X, Wei-Zhong Z (2010) Inhibition of calcium-calmodulin-dependent kinase II suppresses cardiac fibroblast proliferation and extracellular matrix secretion. J Cardiovasc Pharmacol 55:96–105. https://doi.org/10.1097/FJC.0b013e3181c9548b
Xiaowei D, Xia S, Xuefang S, Yan L, Jiaqiang W, Zhirong S, Changhong M, Jiawei C (2019) Propofol attenuates TNF-α-induced MMP-9 expression in human cerebral microvascular endothelial cells by inhibiting Ca/CAMK II/ERK/NF-κB signaling pathway. Acta Pharmacol Sin 40:1303–1313. https://doi.org/10.1038/s41401-019-0258-0
Yamada A, Iwata T, Yamato M, Okano T, Izumi Y (2013) Diverse functions of secreted frizzled-related proteins in the osteoblastogenesis of human multipotent mesenchymal stromal cells. Biomaterials 34:3270–3278. https://doi.org/10.1016/j.biomaterials.2013.01.066
Yamada S, Tauchi T, Awata T, Maeda K, Kajikawa T, Yanagita M, Murakami S (2014) Characterization of a novel periodontal ligament-specific periostin isoform. J Dent Res 93:891–897. https://doi.org/10.1177/0022034514543015
Yamaguchi T, Bradley A, McMahon A, Jones S (1999) A Wnt5a pathway underlies outgrowth of multiple structures in the vertebrate embryo. Dev (Camb, Engl) 126:1211–1223
Yanxin S, Shujuan G, Guoqing C, Yi D, Yafei W, Weidong T (2019) Hyperglycemia induces osteoclastogenesis and bone destruction through the activation of Ca/Calmodulin-dependent protein kinase II. Calcif Tissue Int 104:390–401. https://doi.org/10.1007/s00223-018-0499-9
Zhang Q, Liu J, Ma L, Bai N, Xu H (2019) Wnt5a is involved in LOX-1 and TLR4 induced host inflammatory response in peri-implantitis. J Periodontal Res 55:199–208. https://doi.org/10.1111/jre.12702
Acknowledgements
The work was supported by grants from the National Key Research and Development Program of China (2017YFA0104800) and the Key Research and Development rogram of Sichuan Province (2020YFS0175).
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The work was supported by grants from the National Key Research and Development Program of China (Grant No. 2017YFA0104800) and the Key Research and Development Program of Sichuan Province (Grant No. 2020YFS0175).
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LQ, SG and WT designed the study; LQ, LL, SW and SG performed the experiments; LQ and SG analyzed the data; LQ prepared the first draft of the paper; LQ, SG, HP, YW and WT revised the paper. All authors reviewed and approved the final version. WT and SG were guarantor. All authors agreed to be accountable for the work and to ensure that any questions relating to the accuracy and integrity of the paper was investigated and properly resolved.
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All the experimental procedures containing human periodontal ligament cell culture and animal experiments were approved by the Animal Care and Use Committee and Ethics Committee of West China college of stomatology, Sichuan University (WCHSIRB-D-2017–159).
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Qian, L., Shujuan, G., Ping, H. et al. Wnt5a up-regulates Periostin through CaMKII pathway to influence periodontal tissue destruction in early periodontitis. J Mol Histol 52, 555–566 (2021). https://doi.org/10.1007/s10735-021-09975-z
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DOI: https://doi.org/10.1007/s10735-021-09975-z