inovmedИнновационная медицина КубаниInnovative Medicine of Kuban2541-9897Scientific Research Institute – Ochapovsky Regional Clinical Hospital No. 110.35401/2541-9897-2023-26-2-103-108inovmed-680Research ArticleОБЗОРЫREVIEWSБиохимические аспекты остеорепаративных эффектов магнияBiochemical aspects of magnesium-enhanced bone regenerationhttps://orcid.org/0000-0002-5161-3152БараеваЛ. М.BaraevaL. M.

Бараева Лилия Максимовна, соискатель кафедры фундаментальной и клинической биохимии

350063, Краснодар, ул. им. М. Седина 4

Liliya M. Baraeva, External PhD Candidate, Department of Fundamental and Clinical Biochemistry

ulitsa M. Sedina 4, Krasnodar, 350063, Russian Federation

baraeva-lilia@mail.ruhttps://orcid.org/0000-0002-2927-2734БайдаА. Ш.BaidaA. Sh.

Байда Анна Шамильевна, аспирант кафедры фундаментальной и клинической биохимии

Краснодар

Anna Sh. Baida, Postgraduate Student, Department of Fundamental and Clinical Biochemistry

Krasnodar

https://orcid.org/0000-0002-1787-0040БыковИ. М.BykovI. M.

Быков Илья Михайлович, д. м. н., профессор, заведующий кафедрой фундаментальной и клинической биохимии

Краснодар

Iliya M. Bykov, Dr. Sci. (Med.), Professor, Head of the Department of Fundamental and Clinical Biochemistry

Krasnodar

https://orcid.org/0000-0002-0566-256XКурзановА. Н.KurzanovA. N.

Курзанов Анатолий Николаевич, д. м. н., профессор кафедры фундаментальной и клинической биохимии

Краснодар

Anatoliy N. Kurzanov, Dr. Sci. (Med.), Professor at the Department of Fundamental and Clinical Biochemistry

Krasnodar

https://orcid.org/0000-0002-6203-9272ЦымбаловО. В.TsymbalovO. V.

Цымбалов Олег Владимирович, д. м. н., профессор кафедры хирургической стоматологии и челюстно-лицевой хирургии

Краснодар

Oleg V. Tsymbalov, Dr. Sci. (Med.), Professor at the Department of Surgical Dentistry and Maxillofacial Surgery

Krasnodar

https://orcid.org/0000-0001-8019-9598ПавлюченкоИ. И.PavlyuchenkoI. I.

Павлюченко Иван Иванович, д. м. н., профессор, заведующий кафедрой биологии с курсом медицинской генетики

Краснодар

Ivan I. Pavlyuchenko, Dr. Sci. (Med.), Professor, Head of the Biology Department with Medical Genetics Course

Krasnodar

https://orcid.org/0000-0003-1843-6518СторожукА. П.StorozhukA. P.

Сторожук Александр Петрович, д. м. н., главный врач; профессор кафедры фундаментальной и клинической биохимии

Краснодар

Aleksandr P. Storozhuk, Dr. Sci. (Med.), Chief Physician; Professor at the Department of Fundamental and Clinical Biochemistry

Krasnodar

Кубанский государственный медицинский университетРоссияKuban State Medical UniversityRussian FederationКубанский государственный медицинский университет; Родильный дом г. КраснодараРоссияKuban State Medical University; Krasnodar Maternity HospitalRussian Federation20233006202302103108Copyright © Бараева Л.М., Байда А.Ш., Быков И.М., Курзанов А.Н., Цымбалов О.В., Павлюченко И.И., Сторожук А.П., 20232023Бараева Л.М., Байда А.Ш., Быков И.М., Курзанов А.Н., Цымбалов О.В., Павлюченко И.И., Сторожук А.П.Baraeva L.M., Baida A.S., Bykov I.M., Kurzanov A.N., Tsymbalov O.V., Pavlyuchenko I.I., Storozhuk A.P.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.innovmedkub.ru/jour/article/view/680

Существующий научный и практический интерес к имплантам на основе магния (Mg2+) в значительной степени связан с его биоразлагаемостью и способностью улучшать заживление и формирование костей. Однако основной механизм того как магний регулирует остеогенез до сих пор неясен.

В обзоре рассмотрены клеточные и молекулярные механизмы, лежащие в основе влияния ионов магния на рост новой кости при имплантации устройств на основе этого химического элемента. Представлены данные о Mg-индуцированной активации канонического сигнального пути Wnt/β-Catenin в стромальных клетках костного мозга человека, что, в свою очередь, способствует их дифференцировке в остеобласты и тем самым обеспечивает остеогенный эффект и восстановление костных дефектов. Приведена информация о роли молекулярных механизмов, ответственных за остеопромоторное действие Mg2+, связанных с уникальными катионными каналами TRPM7, опосредующих приток Mg2+, необходимого для влияния фактор роста тромбоцитов, а также на пролиферацию, адгезию и миграцию остеобластов человека и обеспечение Mg2+-ассоциированных остеорегенераторных эффектов.

Кроме того, в обзоре рассмотрено влияние Mg2+ на механизмы внутриклеточной передачи сигналов, экспрессию фактора роста эндотелия сосудов, фактора, индуцируемого гипоксией (HIF)-2α, и гамма-коактиватора рецептора – 1-альфа (PGC-1α), активируемого пролифератором пероксисом.

Таким образом, Mg2+ может способствовать регенерации кости за счет усиления выработки коллагена типа X и фактора роста эндотелия сосудов остеогенными клетками в костной ткани.

Current research is focused on practical implications of magnesium-based implants largely due to their biodegradability and ability to promote bone healing and formation. However, the mechanism underlying the osteogenesis regulation by magnesium is still unclear.

We describe cellular and molecular mechanisms underlying the effect of magnesium ions (Mg2+) on bone growth following the device implantation. The presented data demonstrate magnesium-induced activation of canonical Wnt/β-catenin signaling pathway in human bone marrow stromal cells resulting in their differentiation into osteoblasts, osteogenic effect and recovery of bone defects. We describe the role of the molecular mechanisms responsible for osteopromotive properties of Mg2+ and associated with unique transient receptor potential melastatin 7 (TRPM7) cation channels mediating the Mg2+ influx. TRPM7-mediated Mg2+ influx is important for platelet-derived growth factor (PDGF)-induced proliferation, adhesion, and migration of human osteoblasts, as well as for promotion of Mg2+-associated bone regeneration.

We discuss the effect of Mg2+ on intracellular signaling processes, expression of the vascular endothelial growth factor (VEGF), hypoxia-inducible factor-2α, and peroxisome proliferator-activated receptor-γ coactivator 1α. Mg2+ can promote bone regeneration by enhancing the production of type X collagen and VEGF by osteogenic cells in bone marrow.

магнийремоделирование костиостеобластыостеогенезстволовые клетки костного мозгаmagnesiumbone remodelingosteoblastsosteogenesisbone marrow stromal cellsReferencesSchmitz C, Deason F, Perraud AL. Molecular components of vertebrate Mg2+-homeostasis regulation. Magnes Res. 2007;20(1):6–18. PMID: 17536484.Schmitz C, Deason F, Perraud AL. Molecular components of vertebrate Mg2+-homeostasis regulation. Magnes Res. 2007;20(1):6–18. PMID: 17536484.Zhang Y, Xu J, Ruan YC, et al. Implant-derived magnesium induces local neuronal production of CGRP to improve bone-fracture healing in rats. Nat Med. 2016;22(10):1160–1169. PMID: 27571347. PMCID: PMC5293535. https://doi.org/10.1038/nm.4162Zhang Y, Xu J, Ruan YC, et al. Implant-derived magnesium induces local neuronal production of CGRP to improve bone-fracture healing in rats. Nat Med. 2016;22(10):1160–1169. PMID: 27571347. PMCID: PMC5293535. https://doi.org/10.1038/nm.4162Jähn K, Saito H, Taipaleenmäki H, et al. Intramedullary Mg2Ag nails augment callus formation during fracture healing in mice. Acta Biomater. 2016;36:350–360. PMID: 27039975. https://doi.org/10.1016/j.actbio.2016.03.041Jähn K, Saito H, Taipaleenmäki H, et al. Intramedullary Mg2Ag nails augment callus formation during fracture healing in mice. Acta Biomater. 2016;36:350–360. PMID: 27039975. https://doi.org/10.1016/j.actbio.2016.03.041Chaya A, Yoshizawa S, Verdelis K, et al. In vivo study of magnesium plate and screw degradation and bone fracture healing. Acta Biomater. 2015;18:262–269. PMID: 25712384. https://doi.org/10.1016/j.actbio.2015.02.010Chaya A, Yoshizawa S, Verdelis K, et al. In vivo study of magnesium plate and screw degradation and bone fracture healing. Acta Biomater. 2015;18:262–269. PMID: 25712384. https://doi.org/10.1016/j.actbio.2015.02.010Laires MJ, Monteiro CP, Bicho M. Role of cellular magnesium in health and human disease. Front Biosci. 2004;9:262–276. PMID: 14766364. https://doi.org/10.2741/1223Laires MJ, Monteiro CP, Bicho M. Role of cellular magnesium in health and human disease. Front Biosci. 2004;9:262–276. PMID: 14766364. https://doi.org/10.2741/1223Zhang X, Huang P, Jiang G, et al. A novel magnesium ionincorporating dual-crosslinked hydrogel to improve bone scaffoldmediated osteogenesis and angiogenesis. Mater Sci Eng C Mater Biol Appl. 2021;121:111868. PMID: 33579495. https://doi.org/10.1016/j.msec.2021.111868Zhang X, Huang P, Jiang G, et al. A novel magnesium ionincorporating dual-crosslinked hydrogel to improve bone scaffoldmediated osteogenesis and angiogenesis. Mater Sci Eng C Mater Biol Appl. 2021;121:111868. PMID: 33579495. https://doi.org/10.1016/j.msec.2021.111868Choi S, Kim KJ, Cheon S, et al. Biochemical activity of magnesium ions on human osteoblast migration. Biochem Biophys Res Commun. 2020;531(4):588–594. PMID: 32814632. https://doi.org/10.1016/j.bbrc.2020.07.057Choi S, Kim KJ, Cheon S, et al. Biochemical activity of magnesium ions on human osteoblast migration. Biochem Biophys Res Commun. 2020;531(4):588–594. PMID: 32814632. https://doi.org/10.1016/j.bbrc.2020.07.057Lin S, Yang G, Jiang F, et al. A magnesium-enriched 3D culture system that mimics the bone development microenvironment for vascularized bone regeneration. Adv Sci (Weinh). 2019;6(12):1900209. PMID: 31380166. PMCID: PMC6662069. https://doi.org/10.1002/advs.201900209Lin S, Yang G, Jiang F, et al. A magnesium-enriched 3D culture system that mimics the bone development microenvironment for vascularized bone regeneration. Adv Sci (Weinh). 2019;6(12):1900209. PMID: 31380166. PMCID: PMC6662069. https://doi.org/10.1002/advs.201900209Wang J, Ma XY, Feng YF, et al. Magnesium ions promote the biological behaviour of rat calvarial osteoblasts by activating the PI3K/Akt signalling pathway. Biol Trace Elem Res. 2017;179(2):284–293. PMID: 28205079. https://doi.org/10.1007/s12011-017-0948-8Wang J, Ma XY, Feng YF, et al. Magnesium ions promote the biological behaviour of rat calvarial osteoblasts by activating the PI3K/Akt signalling pathway. Biol Trace Elem Res. 2017;179(2):284–293. PMID: 28205079. https://doi.org/10.1007/s12011-017-0948-8Chen S, Guo Y, Liu R, et al. Tuning surface properties of bone biomaterials to manipulate osteoblastic cell adhesion and the signaling pathways for the enhancement of early osseointegration. Colloids Surf B Biointerfaces. 2018;164:58–69. PMID: 29413621. https://doi.org/10.1016/j.colsurfb.2018.01.022Chen S, Guo Y, Liu R, et al. Tuning surface properties of bone biomaterials to manipulate osteoblastic cell adhesion and the signaling pathways for the enhancement of early osseointegration. Colloids Surf B Biointerfaces. 2018;164:58–69. PMID: 29413621. https://doi.org/10.1016/j.colsurfb.2018.01.022Aubin JE. Advances in the osteoblast lineage. Biochem Cell Biol. 1998;76(6):899–910. PMID: 10392704.Aubin JE. Advances in the osteoblast lineage. Biochem Cell Biol. 1998;76(6):899–910. PMID: 10392704.Mehrotra M, Krane SM, Walters K, Pilbeam C. Differential regulation of platelet-derived growth factor stimulated migration and proliferation in osteoblastic cells. J Cell Biochem. 2004;93(4):741–752. PMID: 15660418. PMID: 15660418. https://doi.org/10.1002/jcb.20138Mehrotra M, Krane SM, Walters K, Pilbeam C. Differential regulation of platelet-derived growth factor stimulated migration and proliferation in osteoblastic cells. J Cell Biochem. 2004;93(4):741–752. PMID: 15660418. PMID: 15660418. https://doi.org/10.1002/jcb.20138Centrella M, McCarthy TL, Canalis E. Platelet-derived growth factor enhances deoxyribonucleic acid and collagen synthesis in osteoblast-enriched cultures from fetal rat parietal bone. Endocrinology. 1989;125(1):13–19. PMID: 2737139. https://doi.org/10.1210/endo-125-1-13Centrella M, McCarthy TL, Canalis E. Platelet-derived growth factor enhances deoxyribonucleic acid and collagen synthesis in osteoblast-enriched cultures from fetal rat parietal bone. Endocrinology. 1989;125(1):13–19. PMID: 2737139. https://doi.org/10.1210/endo-125-1-13Pfeilschifter J, Oechsner M, Naumann A, Gronwald RG, Minne HW, Ziegler R. Stimulation of bone matrix apposition in vitro by local growth factors: a comparison between insulin-like growth factor I, platelet-derived growth factor, and transforming growth factor beta. Endocrinology. 1990;127(1):69–75. PMID: 2361486. https://doi.org/10.1210/endo-127-1-69Pfeilschifter J, Oechsner M, Naumann A, Gronwald RG, Minne HW, Ziegler R. Stimulation of bone matrix apposition in vitro by local growth factors: a comparison between insulin-like growth factor I, platelet-derived growth factor, and transforming growth factor beta. Endocrinology. 1990;127(1):69–75. PMID: 2361486. https://doi.org/10.1210/endo-127-1-69Tanaka H, Wakisaka A, Ogasa H, Kawai S, Liang CT. Effect of IGF-I and PDGF administered in vivo on the expression of osteoblast-related genes in old rats. J Endocrinol. 2002;174(1):63–70. PMID: 12098664. https://doi.org/10.1677/joe.0.1740063Tanaka H, Wakisaka A, Ogasa H, Kawai S, Liang CT. Effect of IGF-I and PDGF administered in vivo on the expression of osteoblast-related genes in old rats. J Endocrinol. 2002;174(1):63–70. PMID: 12098664. https://doi.org/10.1677/joe.0.1740063Rude RK, Kirchen ME, Gruber HE, Meyer MH, Luck JS, Crawford DL. Magnesium deficiency-induced osteoporosis in the rat: uncoupling of bone formation and bone resorption. Magnes Res. 1999;12(4):257–67. PMID: 10612083.Rude RK, Kirchen ME, Gruber HE, Meyer MH, Luck JS, Crawford DL. Magnesium deficiency-induced osteoporosis in the rat: uncoupling of bone formation and bone resorption. Magnes Res. 1999;12(4):257–67. PMID: 10612083.Carpenter TO, Mackowiak SJ, Troiano N, Gundberg CM. Osteocalcin and its message: relationship to bone histology in magnesium-deprived rats. Am J Physiol. 1992;263(1 Pt 1):E107–E114. PMID: 1636687. https://doi.org/10.1152/ajpendo.1992.263.1.E107Carpenter TO, Mackowiak SJ, Troiano N, Gundberg CM. Osteocalcin and its message: relationship to bone histology in magnesium-deprived rats. Am J Physiol. 1992;263(1 Pt 1):E107–E114. PMID: 1636687. https://doi.org/10.1152/ajpendo.1992.263.1.E107Creedon A, Flynn A, Cashman K. The effect of moderately and severely restricted dietary magnesium intakes on bone composition and bone metabolism in the rat. Br J Nutr. 1999;82(1):63–71. PMID: 10655958. https://doi.org/10.1017/s0007114599001130Creedon A, Flynn A, Cashman K. The effect of moderately and severely restricted dietary magnesium intakes on bone composition and bone metabolism in the rat. Br J Nutr. 1999;82(1):63–71. PMID: 10655958. https://doi.org/10.1017/s0007114599001130Abed E, Moreau R. Importance of melastatin-like transient receptor potential 7 and cations (magnesium, calcium) in human osteoblast-like cell proliferation. Cell Prolif. 2007;40(6):849–865. PMID: 18021175. PMCID: PMC6495302. https://doi.org/10.1111/j.1365-2184.2007.00476.xAbed E, Moreau R. Importance of melastatin-like transient receptor potential 7 and cations (magnesium, calcium) in human osteoblast-like cell proliferation. Cell Prolif. 2007;40(6):849–865. PMID: 18021175. PMCID: PMC6495302. https://doi.org/10.1111/j.1365-2184.2007.00476.xFleig A, Penner R. The TRPM ion channel subfamily: molecular, biophysical and functional features. Trends Pharmacol Sci. 2004;25(12):633–639. PMID: 15530641. https://doi.org/10.1016/j.tips.2004.10.004Fleig A, Penner R. The TRPM ion channel subfamily: molecular, biophysical and functional features. Trends Pharmacol Sci. 2004;25(12):633–639. PMID: 15530641. https://doi.org/10.1016/j.tips.2004.10.004Harteneck C. Function and pharmacology of TRPM cation channels. Naunyn Schmiedebergs Arch Pharmacol. 2005; 371(4):307–314. PMID: 15843919. https://doi.org/10.1007/s00210-005-1034-xHarteneck C. Function and pharmacology of TRPM cation channels. Naunyn Schmiedebergs Arch Pharmacol. 2005; 371(4):307–314. PMID: 15843919. https://doi.org/10.1007/s00210-005-1034-xRunnels LW. TRPM6 and TRPM7: A Mul-TRP-PLIK-cation of channel functions. Curr Pharm Biotechnol. 2011;12(1):42–53. PMID: 20932259. PMCID: PMC3514077. https://doi.org/10.2174/138920111793937880Runnels LW. TRPM6 and TRPM7: A Mul-TRP-PLIK-cation of channel functions. Curr Pharm Biotechnol. 2011;12(1):42–53. PMID: 20932259. PMCID: PMC3514077. https://doi.org/10.2174/138920111793937880Krapivinsky G, Krapivinsky L, Manasian Y, Clapham DE. The TRPM7 chanzyme is cleaved to release a chromatin-modifying kinase. Cell. 2014;157(5):1061–1072. PMID: 24855944. PMCID: PMC4156102. https://doi.org/10.1016/j.cell.2014.03.046Krapivinsky G, Krapivinsky L, Manasian Y, Clapham DE. The TRPM7 chanzyme is cleaved to release a chromatin-modifying kinase. Cell. 2014;157(5):1061–1072. PMID: 24855944. PMCID: PMC4156102. https://doi.org/10.1016/j.cell.2014.03.046Abed E, Martineau C, Moreau R. Role of melastatin transient receptor potential 7 channels in the osteoblastic differentiation of murine MC3T3 cells. Calcif Tissue Int. 2011;88(3):246–253. PMID: 21207015. https://doi.org/10.1007/s00223-010-9455-zAbed E, Martineau C, Moreau R. Role of melastatin transient receptor potential 7 channels in the osteoblastic differentiation of murine MC3T3 cells. Calcif Tissue Int. 2011;88(3):246–253. PMID: 21207015. https://doi.org/10.1007/s00223-010-9455-zAbed E, Moreau R. Importance of melastatin-like transient receptor potential 7 and magnesium in the stimulation of osteoblast proliferation and migration by platelet-derived growth factor. Am J Physiol Cell Physiol. 2009;297(2):C360–C368. PMID: 19474290. https://doi.org/10.1152/ajpcell.00614.2008Abed E, Moreau R. Importance of melastatin-like transient receptor potential 7 and magnesium in the stimulation of osteoblast proliferation and migration by platelet-derived growth factor. Am J Physiol Cell Physiol. 2009;297(2):C360–C368. PMID: 19474290. https://doi.org/10.1152/ajpcell.00614.2008Kusumbe AP, Ramasamy SK, Adams RH. Coupling of angiogenesis and osteogenesis by a specific vessel subtype in bone. Nature. 2014;507(7492):323–328. PMID: 24646994. PMCID: PMC4943525. https://doi.org/10.1038/nature13145Kusumbe AP, Ramasamy SK, Adams RH. Coupling of angiogenesis and osteogenesis by a specific vessel subtype in bone. Nature. 2014;507(7492):323–328. PMID: 24646994. PMCID: PMC4943525. https://doi.org/10.1038/nature13145Maes C, Goossens S, Bartunkova S, et al. Increased skeletal VEGF enhances beta-catenin activity and results in excessively ossified bones. EMBO J. 2010;29(2):424–441. PMID: 20010698. PMCID: PMC2824461. https://doi.org/10.1038/emboj.2009.361Maes C, Goossens S, Bartunkova S, et al. Increased skeletal VEGF enhances beta-catenin activity and results in excessively ossified bones. EMBO J. 2010;29(2):424–441. PMID: 20010698. PMCID: PMC2824461. https://doi.org/10.1038/emboj.2009.361Maes C, Kobayashi T, Selig MK, et al. Osteoblast precursors, but not mature osteoblasts, move into developing and fractured bones along with invading blood vessels. Dev Cell. 2010;19(2):329–344. PMID: 20708594. PMCID: PMC3540406. https://doi.org/10.1016/j.devcel.2010.07.010Maes C, Kobayashi T, Selig MK, et al. Osteoblast precursors, but not mature osteoblasts, move into developing and fractured bones along with invading blood vessels. Dev Cell. 2010;19(2):329–344. PMID: 20708594. PMCID: PMC3540406. https://doi.org/10.1016/j.devcel.2010.07.010Lee JW, Han HS, Han KJ, et al. Long-term clinical study and multiscale analysis of in vivo biodegradation mechanism of Mg alloy. Proc Natl Acad Sci U S A. 2016;113(3):716–721. PMID: 26729859. PMCID: PMC4725539. https://doi.org/10.1073/pnas.1518238113Lee JW, Han HS, Han KJ, et al. Long-term clinical study and multiscale analysis of in vivo biodegradation mechanism of Mg alloy. Proc Natl Acad Sci U S A. 2016;113(3):716–721. PMID: 26729859. PMCID: PMC4725539. https://doi.org/10.1073/pnas.1518238113Riddle RC, Khatri R, Schipani E, Clemens TL. Role of hypoxia-inducible factor-1alpha in angiogenic-osteogenic coupling. J Mol Med (Berl). 2009;87(6):583–590. PMID: 19415227. PMCID: PMC3189695. https://doi.org/10.1007/s00109-009-0477-9Riddle RC, Khatri R, Schipani E, Clemens TL. Role of hypoxia-inducible factor-1alpha in angiogenic-osteogenic coupling. J Mol Med (Berl). 2009;87(6):583–590. PMID: 19415227. PMCID: PMC3189695. https://doi.org/10.1007/s00109-009-0477-9Han HS, Jun I, Seok HK, et al. Biodegradable magnesium alloys promote angio-osteogenesis to enhance bone repair. Adv Sci (Weinh). 2020;7(15):2000800. PMID: 32775162. PMCID: PMC7404158. https://doi.org/10.1002/advs.202000800Han HS, Jun I, Seok HK, et al. Biodegradable magnesium alloys promote angio-osteogenesis to enhance bone repair. Adv Sci (Weinh). 2020;7(15):2000800. PMID: 32775162. PMCID: PMC7404158. https://doi.org/10.1002/advs.202000800Hung CC, Chaya A, Liu K, Verdelis K, Sfeir C. The role of magnesium ions in bone regeneration involves the canonical Wnt signaling pathway. Acta Biomater. 2019;98:246–255. PMID: 31181262. https://doi.org/10.1016/j.actbio.2019.06.001Hung CC, Chaya A, Liu K, Verdelis K, Sfeir C. The role of magnesium ions in bone regeneration involves the canonical Wnt signaling pathway. Acta Biomater. 2019;98:246–255. PMID: 31181262. https://doi.org/10.1016/j.actbio.2019.06.001Meng Z, Feng G, Hu X, Yang L, Yang X, Jin Q. SDF factor- 1α promotes the migration, proliferation, and osteogenic differentiation of mouse bone marrow mesenchymal stem cells through the Wnt/β-catenin pathway. Stem Cells Dev. 2021;30(2):106–117. PMID: 33234049. https://doi.org/10.1089/scd.2020.0165Meng Z, Feng G, Hu X, Yang L, Yang X, Jin Q. SDF factor- 1α promotes the migration, proliferation, and osteogenic differentiation of mouse bone marrow mesenchymal stem cells through the Wnt/β-catenin pathway. Stem Cells Dev. 2021;30(2):106–117. PMID: 33234049. https://doi.org/10.1089/scd.2020.0165Zhao W, Jin K, Li J, Qiu X, Li S. Delivery of stromal cell-derived factor 1α for in situ tissue regeneration. J Biol Eng. 2017;11(1):22. PMID: 28670340. PMCID: PMC5492719. https://doi.org/10.1186/s13036-017-0058-3Zhao W, Jin K, Li J, Qiu X, Li S. Delivery of stromal cell-derived factor 1α for in situ tissue regeneration. J Biol Eng. 2017;11(1):22. PMID: 28670340. PMCID: PMC5492719. https://doi.org/10.1186/s13036-017-0058-3Cencioni C, Capogrossi MC, Napolitano M. The SDF-1/CXCR4 axis in stem cell preconditioning. Cardiovasc Res. 2012;94(3):400–407. PMID: 22451511. https://doi.org/10.1093/cvr/cvs132Cencioni C, Capogrossi MC, Napolitano M. The SDF-1/CXCR4 axis in stem cell preconditioning. Cardiovasc Res. 2012;94(3):400–407. PMID: 22451511. https://doi.org/10.1093/cvr/cvs132Li L, Liu X, Gaihre B, et al. SDF-1α/OPF/BP composites enhance the migrating and osteogenic abilities of mesenchymal stem cells. Stem Cells Int. 2021;2021:1938819. PMID: 34434236. PMCID: PMC8380507. https://doi.org/10.1155/2021/1938819Li L, Liu X, Gaihre B, et al. SDF-1α/OPF/BP composites enhance the migrating and osteogenic abilities of mesenchymal stem cells. Stem Cells Int. 2021;2021:1938819. PMID: 34434236. PMCID: PMC8380507. https://doi.org/10.1155/2021/1938819Liang Q, Du L, Zhang R, Kang W, Ge S. Stromal cellderived factor-1/Exendin-4 cotherapy facilitates the proliferation, migration and osteogenic differentiation of human periodontal ligament stem cells in vitro and promotes periodontal bone regeneration in vivo. Cell Prolif. 2021;54(3):e12997. PMID: 33511708. PMCID: PMC7941242. https://doi.org/10.1111/cpr.12997Liang Q, Du L, Zhang R, Kang W, Ge S. Stromal cellderived factor-1/Exendin-4 cotherapy facilitates the proliferation, migration and osteogenic differentiation of human periodontal ligament stem cells in vitro and promotes periodontal bone regeneration in vivo. Cell Prolif. 2021;54(3):e12997. PMID: 33511708. PMCID: PMC7941242. https://doi.org/10.1111/cpr.12997Marquez-Curtis LA, Janowska-Wieczorek A. Enhancing the migration ability of mesenchymal stromal cells by targeting the SDF-1/CXCR4 axis. Biomed Res Int. 2013;2013:561098. PMID: 24381939. PMCID: PMC3870125. https://doi.org/10.1155/2013/561098Marquez-Curtis LA, Janowska-Wieczorek A. Enhancing the migration ability of mesenchymal stromal cells by targeting the SDF-1/CXCR4 axis. Biomed Res Int. 2013;2013:561098. PMID: 24381939. PMCID: PMC3870125. https://doi.org/10.1155/2013/561098Xu M, Wei X, Fang J, Xiao L. Combination of SDF-1 and bFGF promotes bone marrow stem cell-mediated periodontal ligament regeneration. Biosci Rep. 2019;39(12):BSR20190785. PMID: 31789340. PMCID: PMC6923350. https://doi.org/10.1042/BSR20190785Xu M, Wei X, Fang J, Xiao L. Combination of SDF-1 and bFGF promotes bone marrow stem cell-mediated periodontal ligament regeneration. Biosci Rep. 2019;39(12):BSR20190785. PMID: 31789340. PMCID: PMC6923350. https://doi.org/10.1042/BSR20190785Hosogane N, Huang Z, Rawlins BA, et al. Stromal derived factor-1 regulates bone morphogenetic protein 2-induced osteogenic differentiation of primary mesenchymal stem cells. Int J Biochem Cell Biol. 2010;42(7):1132–1141. PMID: 20362069. PMCID: PMC2992806. https://doi.org/10.1016/j.biocel.2010.03.020Hosogane N, Huang Z, Rawlins BA, et al. Stromal derived factor-1 regulates bone morphogenetic protein 2-induced osteogenic differentiation of primary mesenchymal stem cells. Int J Biochem Cell Biol. 2010;42(7):1132–1141. PMID: 20362069. PMCID: PMC2992806. https://doi.org/10.1016/j.biocel.2010.03.020Xia B, Deng Y, Lv Y, Chen G. Stem cell recruitment based on scaffold features for bone tissue engineering. Biomater Sci. 2021;9(4):1189–1203. PMID: 33355545. https://doi.org/10.1039/d0bm01591aXia B, Deng Y, Lv Y, Chen G. Stem cell recruitment based on scaffold features for bone tissue engineering. Biomater Sci. 2021;9(4):1189–1203. PMID: 33355545. https://doi.org/10.1039/d0bm01591aBai X, Gao M, Syed S, Zhuang J, Xu X, Zhang XQ. Bioactive hydrogels for bone regeneration. Bioact Mater. 2018;3(4):401–417. PMID: 30003179. PMCID: PMC6038268. https://doi.org/10.1016/j.bioactmat.2018.05.006Bai X, Gao M, Syed S, Zhuang J, Xu X, Zhang XQ. Bioactive hydrogels for bone regeneration. Bioact Mater. 2018;3(4):401–417. PMID: 30003179. PMCID: PMC6038268. https://doi.org/10.1016/j.bioactmat.2018.05.006Xiao M, Qiu J, Kuang R, Zhang B, Wang W, Yu Q. Synergistic effects of stromal cell-derived factor-1α and bone morphogenetic protein-2 treatment on odontogenic differentiation of human stem cells from apical papilla cultured in the VitroGel 3D system. Cell Tissue Res. 2019;378(2):207–220. PMID: 31152245. https://doi.org/10.1007/s00441-019-03045-3Xiao M, Qiu J, Kuang R, Zhang B, Wang W, Yu Q. Synergistic effects of stromal cell-derived factor-1α and bone morphogenetic protein-2 treatment on odontogenic differentiation of human stem cells from apical papilla cultured in the VitroGel 3D system. Cell Tissue Res. 2019;378(2):207–220. PMID: 31152245. https://doi.org/10.1007/s00441-019-03045-3Holloway JL, Ma H, Rai R, Hankenson KD, Burdick JA. Synergistic effects of SDF-1α and BMP-2 delivery from proteolytically degradable hyaluronic acid hydrogels for bone repair. Macromol Biosci. 2015;15(9):1218–1223. PMID: 26059079. PMCID: PMC4558375. https://doi.org/10.1002/mabi.201500178Holloway JL, Ma H, Rai R, Hankenson KD, Burdick JA. Synergistic effects of SDF-1α and BMP-2 delivery from proteolytically degradable hyaluronic acid hydrogels for bone repair. Macromol Biosci. 2015;15(9):1218–1223. PMID: 26059079. PMCID: PMC4558375. https://doi.org/10.1002/mabi.201500178Li Z, Lin H, Shi S, et al. Controlled and sequential delivery of stromal derived factor-1 α (SDF-1α) and magnesium ions from bifunctional hydrogel for bone regeneration. Polymers (Basel). 2022;14(14):2872. PMID: 35890649. PMCID: PMC9315491. https://doi.org/10.3390/polym14142872Li Z, Lin H, Shi S, et al. Controlled and sequential delivery of stromal derived factor-1 α (SDF-1α) and magnesium ions from bifunctional hydrogel for bone regeneration. Polymers (Basel). 2022;14(14):2872. PMID: 35890649. PMCID: PMC9315491. https://doi.org/10.3390/polym14142872Yoshizawa S, Brown A, Barchowsky A, Sfeir C. Role of magnesium ions on osteogenic response in bone marrow stromal cells. Connect Tissue Res. 2014;55(Suppl 1):155–159. PMID: 25158202. https://doi.org/10.3109/03008207.2014.923877Yoshizawa S, Brown A, Barchowsky A, Sfeir C. Role of magnesium ions on osteogenic response in bone marrow stromal cells. Connect Tissue Res. 2014;55(Suppl 1):155–159. PMID: 25158202. https://doi.org/10.3109/03008207.2014.923877Yoshizawa S, Brown A, Barchowsky A, Sfeir C. Magnesium ion stimulation of bone marrow stromal cells enhances osteogenic activity, simulating the effect of magnesium alloy degradation. Acta Biomater. 2014;10(6):2834–2842. PMID: 24512978. https://doi.org/10.1016/j.actbio.2014.02.002Yoshizawa S, Brown A, Barchowsky A, Sfeir C. Magnesium ion stimulation of bone marrow stromal cells enhances osteogenic activity, simulating the effect of magnesium alloy degradation. Acta Biomater. 2014;10(6):2834–2842. PMID: 24512978. https://doi.org/10.1016/j.actbio.2014.02.002Qi T, Weng J, Yu F, et al. Insights into the role of magnesium ions in affecting osteogenic differentiation of mesenchymal stem cells. Biol Trace Elem Res. 2021;199(2):559–567. PMID: 32449009. https://doi.org/10.1007/s12011-020-02183-yQi T, Weng J, Yu F, et al. Insights into the role of magnesium ions in affecting osteogenic differentiation of mesenchymal stem cells. Biol Trace Elem Res. 2021;199(2):559–567. PMID: 32449009. https://doi.org/10.1007/s12011-020-02183-yZhou CC, Wu ZP, Zou SJ. The study of signal pathway regulating the osteogenic differentiation of bone marrow mesenchymal stem cells. Sichuan Da Xue Xue Bao Yi Xue Ban. 2020;51(6):777–782. (In Chinese). PMID: 33236600.Zhou CC, Wu ZP, Zou SJ. The study of signal pathway regulating the osteogenic differentiation of bone marrow mesenchymal stem cells. Sichuan Da Xue Xue Bao Yi Xue Ban. 2020;51(6):777–782. (In Chinese). PMID: 33236600.

The authors declare that there are no conflicts of interest present.