Abstract
Osteoporosis occurs frequently in women after menopause and old age, and it is very easy to cause osteoporotic fractures, resulting in disability and death. In osteoporosis patients, the potential of bone marrow mesenchymal stem cells (BMSCs) to differentiate into osteoblasts gradually is inhibited, leading to decreased new bone formation. In the current study, the potential effect of G-protein-coupled receptor 124 (GPR124) on the osteoblastic differentiation of BMSCs was determined. BMSCs were isolated and cultured in osteogenic media to induced osteogenic differentiation. Then, osteogenic differentiation was evaluated by Alizarin Red staining and ALP activity. The expression of osteogenic differentiation biomarkers, and Wnt/β-catenin signaling were determined by qRT-PCR and Western blotting. The results indicated that the expression of GPR124 was significantly increased during osteogenic differentiation of BMSCs. Moreover, GPR124 knockdown significantly inhibited osteoblastic differentiation and GPR124 overexpression promoted osteoblastic differentiation of BMSCs. GPR124 knockdown suppressed the activation of Wnt/β-catenin signaling pathway. What’s more, the increased osteogenic differentiation induced by GPR124 overexpression was abolished by the inhibitor of Wnt/β-catenin pathway and Wnt7a knockdown. Taken together, GPR124 promotes osteogenic differentiation of BMSCs through the Wnt/β-catenin pathway and may serve as a potential target for enhancing osteogenesis of osteoporosis patients.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Adami S (2008) Full length parathyroid hormone, PTH(1–84), for the treatment of severe osteoporosis in postmenopausal women. Curr Med Res Opin 24:3259–3274. https://doi.org/10.1185/03007990802518130
Aspray TJ, Hill TR (2019) Osteoporosis and the ageing skeleton. Subcell Biochem 91:453–476. https://doi.org/10.1007/978-981-13-3681-2_16
Eastell R, O’Neill TW, Hofbauer LC, Langdahl B, Reid IR, Gold DT, Cummings SR (2016) Postmenopausal osteoporosis. Nat Rev Dis Primers 2:16069. https://doi.org/10.1038/nrdp.2016.69
Houschyar KS, Tapking C, Borrelli MR, Popp D, Duscher D, Maan ZN, Chelliah MP, Li J, Harati K, Wallner C, Rein S, Pförringer D, Reumuth G, Grieb G, Mouraret S, Dadras M, Wagner JM, Cha JY, Siemers F, Lehnhardt M, Behr B (2018) Wnt pathway in bone repair and regeneration - what do we know so far. Front Cell Dev Biol 6:170. https://doi.org/10.3389/fcell.2018.00170
Hwang SY, Deng X, Byun S, Lee C, Lee SJ, Suh H, Zhang J, Kang Q, Zhang T, Westover KD, Mandinova A, Lee SW (2016) Direct targeting of β-catenin by a small molecule stimulates proteasomal degradation and suppresses oncogenic Wnt/β-catenin signaling. Cell Rep 16:28–36. https://doi.org/10.1016/j.celrep.2016.05.071
Jin Z, Chen J, Shu B, Xiao Y, Tang D (2019) Bone mesenchymal stem cell therapy for ovariectomized osteoporotic rats: a systematic review and meta-analysis. BMC Musculoskelet Disord 20:556. https://doi.org/10.1186/s12891-019-2851-2
Kim JM, Lin C, Stavre Z, Greenblatt MB, Shim JH (2020) Osteoblast-osteoclast communication and bone homeostasis. Cells 9:2073. https://doi.org/10.3390/cells9092073
Korvala J, Jüppner H, Mäkitie O, Sochett E, Schnabel D, Mora S, Bartels CF, Warman ML, Deraska D, Cole WG, Hartikka H, Ala-Kokko L, Männikkö M (2012) Mutations in LRP5 cause primary osteoporosis without features of OI by reducing Wnt signaling activity. BMC Med Genet 13:26. https://doi.org/10.1186/1471-2350-13-26
Kraenzlin ME, Meier C (2011) Parathyroid hormone analogues in the treatment of osteoporosis. Nat Rev Endocrinol 7:647–656. https://doi.org/10.1038/nrendo.2011.108
Kugimiya F, Kawaguchi H, Ohba S, Kawamura N, Hirata M, Chikuda H, Azuma Y, Woodgett JR, Nakamura K, Chung UI (2007) GSK-3beta controls osteogenesis through regulating Runx2 activity. PLoS ONE 2:e837. https://doi.org/10.1371/journal.pone.0000837
MacDonald BT, Tamai K, He X (2009) Wnt/beta-catenin signaling: components, mechanisms, and diseases. Dev Cell 17:9–26. https://doi.org/10.1016/j.devcel.2009.06.016
Martin M, Vermeiren S, Bostaille N, Eubelen M, Spitzer D, Vermeersch M, Profaci CP, Pozuelo E, Toussay X, Raman-Nair J, Tebabi P, America M, De Groote A, Sanderson LE, Cabochette P, Germano RFV, Torres D, Boutry S, de Kerchoved’Exaerde A, Bellefroid EJ, Phoenix TN, Devraj K, Lacoste B, Daneman R, Liebner S, Vanhollebeke B (2022) Engineered Wnt ligands enable blood-brain barrier repair in neurological disorders. Science 375:eabm4459. https://doi.org/10.1126/science.abm4459
Pavone V, Testa G, Giardina SMC, Vescio A, Restivo DA, Sessa G (2017) Pharmacological therapy of osteoporosis: a systematic current review of literature. Front Pharmacol 8:803. https://doi.org/10.3389/fphar.2017.00803
Posokhova E, Shukla A, Seaman S, Volate S, Hilton MB, Wu B, Morris H, Swing DA, Zhou M, Zudaire E, Rubin JS, St Croix B (2015) GPR124 functions as a WNT7-specific coactivator of canonical β-catenin signaling. Cell Rep 10:123–130. https://doi.org/10.1016/j.celrep.2014.12.020
Ren W, Gan D, Tan G, Xue H, Li N, Xu Z (2020) Changes in Wnt/B-catenin signaling and differentiation potential of bone marrow mesenchymal stem cells in process of bone loss in ovariectomized rats. Acta Endocrinol (Buchar) 16:156–164. https://doi.org/10.4183/aeb.2020.156
Shen G, Ren H, Shang Q, Zhao W, Zhang Z, Yu X, Tang K, Tang J, Yang Z, Liang D, Jiang X (2020) Foxf1 knockdown promotes BMSC osteogenesis in part by activating the Wnt/β-catenin signalling pathway and prevents ovariectomy-induced bone loss. EBioMedicine 52:102626. https://doi.org/10.1016/j.ebiom.2020.102626
St Croix B, Rago C, Velculescu V, Traverso G, Romans KE, Montgomery E, Lal A, Riggins GJ, Lengauer C, Vogelstein B, Kinzler KW (2000) Genes expressed in human tumor endothelium. Science 289:1197–1202. https://doi.org/10.1126/science.289.5482.1197
Sui X, Deng S, Liu M, Fan L, Wang Y, Xu H, Sun Y, Kishen A, Zhang Q (2018) Constitutive activation of β-catenin in differentiated osteoclasts induces bone loss in mice. Cell Physiol Biochem 48:2091–2102. https://doi.org/10.1159/000492549
Wang R, Zhang Y, Jin F, Li G, Sun Y, Wang X (2019) High-glucose-induced miR-214-3p inhibits BMSCs osteogenic differentiation in type 1 diabetes mellitus. Cell Death Discov 5:143. https://doi.org/10.1038/s41420-019-0223-1
Wang Y, Cho SG, Wu X, Siwko S, Liu M (2014) G-protein coupled receptor 124 (GPR124) in endothelial cells regulates vascular endothelial growth factor (VEGF)-induced tumor angiogenesis. Curr Mol Med 14:543–554. https://doi.org/10.2174/1566524014666140414205943
Yang L, Li Q, Zhang J, Li P, An P, Wang C, Hu P, Zou X, Dou X, Zhu L (2021) Wnt7a promotes the osteogenic differentiation of human mesenchymal stem cells. Int J Mol Med 47. https://doi.org/10.3892/ijmm.2021.4927
Yuan F, Peng W, Yang C, Zheng J (2019) Teriparatide versus bisphosphonates for treatment of postmenopausal osteoporosis: a meta-analysis. Int J Surg 66:1–11. https://doi.org/10.1016/j.ijsu.2019.03.004
Zhang W, Chen E, Chen M, Ye C, Qi Y, Ding Q, Li H, Xue D, Gao X, Pan Z (2018) IGFBP7 regulates the osteogenic differentiation of bone marrow-derived mesenchymal stem cells via Wnt/β-catenin signaling pathway. Faseb j 32:2280–2291. https://doi.org/10.1096/fj.201700998RR
Zhou Y, Nathans J (2014) Gpr124 controls CNS angiogenesis and blood-brain barrier integrity by promoting ligand-specific canonical wnt signaling. Dev Cell 31:248–256. https://doi.org/10.1016/j.devcel.2014.08.018
Zhu Y, Wang Y, Jia Y, Xu J, Chai Y (2019) Catalpol promotes the osteogenic differentiation of bone marrow mesenchymal stem cells via the Wnt/β-catenin pathway. Stem Cell Res Ther 10:37. https://doi.org/10.1186/s13287-019-1143-y
Author information
Authors and Affiliations
Contributions
WR designed the study and supervised the data collection. MJW and CP performed the experiments and prepared the manuscript. All authors have read and approved the manuscript.
Corresponding author
Ethics declarations
Ethics approval
All the experimental procedures were approved by the Ethics Committee of The First Hospital of Yulin.
Data availability
Data will be made available on reasonable request.
Conflict of interest
The authors declare no competing interests.
Rights and permissions
About this article
Cite this article
Ma, J., Chen, P. & Wang, R. G-protein-coupled receptor 124 promotes osteogenic differentiation of BMSCs through the Wnt/β-catenin pathway. In Vitro Cell.Dev.Biol.-Animal 58, 529–538 (2022). https://doi.org/10.1007/s11626-022-00684-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11626-022-00684-9