https://doi.org/10.4081/ejh.2020.3183
Role of Zip1 in the regulation of NPY expression by MLT to promote fracture healing in rats
Submitted: 28 September 2020
Accepted: 5 November 2020
Published: 2 December 2020
Accepted: 5 November 2020
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All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Authors
Our previous study documented that melatonin (MLT) induced the osteogenic differentiation of mesenchymal stem cells (MSCs) and promoted the healing of femoral fractures in rats via the neuropeptide Y (NPY)/neuropeptide Y1 receptor (NPY1R) signaling pathway. MLT treatment upregulated the expression of the zinc uptake transporter zinc transporter 1 (Zip1) in nerve cells. Prior research demonstrated that oral zinc upregulated NPY expression. MSCs were isolated from rat bone marrow and identified using flow cytometry in our study. The results showed that MLT treatment upregulated NPY and NPY1R levels in MSCs with osteogenic differentiation, which was accompanied by upregulated Zip1 expression. However, the MLT-induced osteogenic differentiation of MSCs was reversed after interference of Zip1 expression. It was confirmed by the decreased alkaline phosphatase (ALP) level; downregulated activities of type I collagen α1 chain (COL1A1), osteocalcin (OCN), runt-related transcription factor 2 (Runx2) and ALP; and reduced mineralized nodule formation. MLT promoted fracture healing in rats with femoral fracture, which was accompanied by increased expression of NPY and NPY1R and significantly increased expression of Zip1. In contrast, the silencing of Zip1 expression reversed MLT-mediated fracture healing. In summary, Zip1 participated in the regulation of the NPY/NPY1R signaling pathway via MLT to promote the osteogenic differentiation of MSCs and fracture healing.
Amstrup AK, Sikjaer T, Heickendorff L, Mosekilde L, Rejnmark L.Melatonin improves bone mineral density at the femoral neck in postmenopausal women with osteopenia:a randomized controlled trial. J Pineal Res 2015;59:221-9.
Koerner JD, Vives MJ, O'Connor JP, Chirichella P, Breitbart EA, Chaudhary SB, et al. Zinc has insulin-mimetic properties which enhance spinal fusion in a rat model. Spine 2016;16 777-83.
Gaither L A, Eide D J. The human ZIP1 transporter mediates zinc uptake in human K562 erythroleukemia cells. J Biol Chem 2001;276:22258-64.
Kessels JE, Wessels I, Haase H, Rink L, Uciechowski P. Influence of DNA-methylation on zinc homeostasis in myeloid cells: Regulation of zinc transporters and zinc binding proteins. J Trace Elem Med Biol 2016;37:125-33.
Tang Z, Sahu SN, Khadeer MA, Bai G, Franklin RB, Gupta A. Overexpression of the ZIP1 zinc transporter induces an osteogenic phenotype in mesenchymal stem cells. Bone 2006;38:181-98.
Costello LC, Chellaiah MA, Zou J, Reynolds MA, Franklin RB. In vitro BMP2 stimulation of osteoblast citrate production in concert with mineralized bone nodule formation. J Regen Med Tissue Eng 2015;4:2.
Liu XW,Zi Y,Liu YE,Zhang YB,Xiang LB,Hou MX.Melatonin exerts protective effect on N2a cells under hypoxia conditions through Zip1/ERK pathway. Neurosci Lett 2015;595:74-80.
Ohinata K, Takemoto M, Kawanago M, Fushimi S, Shirakawa H, Goto T, et al. Orally administered zinc increases food intake via vagal stimulation in rats. J Nutr 2009;139:611-6.
Dong P, Gu X, Zhu G, Li M, Ma B, Zi Y. Melatonin induces osteoblastic differentiation of mesenchymal stem cells and promotes fracture healing in a rat model of femoral fracture via neuropeptide Y/neuropeptide Y receptor Y1 signaling. Pharmacology 2018;102:272-80.
Long Q, Luo Q, Wang K, Bates A, Shetty AK. Mash1-dependent notch signaling pathway regulates GABAergic neuron-like differentiation from bone marrow-derived mesenchymal stem cells. Aging Dis 2017;8:301-13.
Gong Yu, Wang H, Xia H. Stable transfection into rat bone marrow mesenchymal stem cells by lentivirus-mediatedNT-3. Mol Med Rep 2015;11:367-73.
Halici M, Oner M, Guney A, Canoz O, Narin F, Halici C. Melatonin promotes fracture healing in the rat model. Eklem Hastalik Cerrahisi 2010;21:172-7.
Xue D, Zhang W, Chen E, Gao X, Liu L, Ye C, et al. Local delivery of HMGB1 in gelatin sponge scaffolds combined with mesenchymal stem cell sheets to accelerate fracture healing. Oncotarget 2017;8:42098-115.
Gao F, Zhang CQ, Chai YM, Li XL. Lentivirus-mediated Wnt10b overexpression enhances fracture healing in a rat atrophic non-union model. Biotechnol Lett 2015;37:733‐9.
Radio NM, Doctor JS, Witt-Enderby PA. Melatonin enhances alkaline phosphatase activity in differentiating human adult mesenchymal stem cells grown in osteogenic medium via MT2 melatonin receptors and the MEK/ERK (1/2) signaling cascade. J Pineal Res 2006;40:332-42.
Calvo-Guirado JL, Gomez-Moreno G, Mate-Sanchez JE, Lopez-Mari L, Delgado-Ruiz R, Romanos GE. New bone formation in bone defects after melatonin and porcine bone grafts: experimental study in rabbits. Clin Oral Implants Res 2015;26:399-406.
Sugiyama O, An DS, Kung SP, Feeley BT, Gamradt S, Liu NQ, et al. Lentivirus-mediated gene transfer induces long-term transgene expression of BMP-2 in vitro and new bone formation in vivo. Mol Ther 2005;11:390-8.
Xu XL, Tang T, Dai K, Zhu Zh, Guo XE, Yu Ch, et al. Immune response and effect of adenovirus-mediated human BMP-2 gene transfer on the repair of segmental tibial bone defects in goats. Acta Orthop 2005;76:637-46.
Lieberman JR, Daluiski A, Stevenson S, Wu L, McAllister P, Lee YP, et al. The effect of regional gene therapy with bone morphogenetic protein-2-producing bone-marrow cells on the repair of segmental femoral defects in rats. J Bone Joint Surg Am 1999;81:905-17.
Virk MS, Conduah A, Park SH, Liu N, Sugiyama O, Cuomo A, et al.Influence of short-term adenoviral vector and prolonged lentiviral vector mediated bone morphogenetic protein-2 expression on the quality of bone repair in a rat femoral defect model. Bone 2008;42:921-31.
Su JG, Zhu ZY, Wang Y, Xiong F, Zou J.The cyto-megalovirus promoter-driven short hairpin RNA constructs mediate effective RNA interference in zebrafish in vivo. Mar Biotechnol 2008;10:262-9.
Zhang W, Zhang X, Ling J, Wei X, Jian Y. Osteo-/odontogenic differentiation of BMP2 and VEGF gene-co-transfected human stem cells from apical papilla. Mol Med Rep 2016;13:3747-54.
Lin Z, Wang JS, Lin L, Zhang J, Liu Y, Shuai M, et al. Effects of BMP2 and VEGF165 on the osteogenic differentiation of rat bone marrow-derived mesenchymal stem cells. Exp Ther Med 2014;7:625-9.
Wang Y, He T, Liu J, Liu H, Zhou L, Hao W, et al. Synergistic effects of overexpression of BMP2 and TGFbeta3 on osteogenic differentiation of bone marrow mesenchymal stem cells. Mol Med Rep 2016;14:5514-20.
Hsu WK, Sugiyama O, Park SH, Conduah A, Feeley BT, Liu NQ, et al. Lentiviral-mediated BMP-2 gene transfer enhances healing of segmental femoral defects in rats. Bone 2007;40:931-8.
Naldini L, Blomer U, Gallay P, Ory D, Mulligan R, Gage FH, et al. In vivo gene delivery and stable transduction of nondividing cells by a lentiviral vector. Science 1996;272:263-7.
Schindeler A, McDonald MM, Bokko P, Little DG. Bone remodeling during fracture repair: the cellular picture. Semin Cell Dev Biol 2008;19:459-66.
Iwaki A, Jinguishi S, Oda Y, Izumi T, Shida J-I, Tsuneyoshi M, et al. Localization and quantification of proliferating cells during rat fracture repair: detection of proliferating cell nuclear antigen by immunohistochemistry. J Bone Miner Res 1997;12:96-102.
Rundle CH, Miyakoshi N, Kasukawa Y, Chen S, Sheng Matilda H-C, Wergedal JE, et al. In vivo bone formation in fracture repair induced by direct retroviral-based gene therapy with bone morphogenetic protein-4. Bone 2003;32:591-601.
Suzuki T, Katsumata S, Matsuzaki H. A short-term zinc-deficient diet decreases bone formation through down-regulated BMP2 in rat bone. Biosci Biotechnol Biochem 2016;80:1433-5.
Wang Xinling, Li Guicai, Zhang Hua, Cui Yong. Comparison of bone mineral density and serum trace elements between Uygur young and elderly women in Urumqi. Chinese J Tissue Engin Res 2015;19:5264-8.
How to Cite
Shang, J. ., Ma, B. ., Zhu, G. ., Dong, P. ., Wang, C. ., Gu, X., & Zi, Y. . (2020). Role of Zip1 in the regulation of NPY expression by MLT to promote fracture healing in rats. European Journal of Histochemistry, 64(s2). https://doi.org/10.4081/ejh.2020.3183
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