CD41-deficient exosomes from non-traumatic femoral head necrosis tissues impair osteogenic differentiation and migration of mesenchymal stem cells.
Journal
Cell death & disease
ISSN: 2041-4889
Titre abrégé: Cell Death Dis
Pays: England
ID NLM: 101524092
Informations de publication
Date de publication:
27 04 2020
27 04 2020
Historique:
received:
02
01
2020
accepted:
10
04
2020
revised:
09
04
2020
entrez:
29
4
2020
pubmed:
29
4
2020
medline:
1
4
2021
Statut:
epublish
Résumé
Non-traumatic osteonecrosis of the femoral head (ONFH) is clinically a devastating and progressive disease without an effective treatment. Mesenchymal stem cells (MSCs) transplantation has been used to treat ONFH in early stage, but the failure rate of this therapy is high due to the reduced osteogenic differentiation and migration of the transplanted MSCs related with pathological bone tissues. However, the mechanism responsible for this decrease is still unclear. Therefore, we assume that the implanted MSCs might be influenced by signals delivered from pathological bone tissue, where the exosomes might play a critical role in this delivery. This study showed that exosomes from ONFH bone tissues (ONFH-exos) were able to induce GC-induced ONFH-like damage, in vivo and impair osteogenic differentiation and migration of MSCs, in vitro. Then, we analyzed the differentially expressed proteins (DEPs) in ONFH-exos using proteomic technology and identified 842 differentially expressed proteins (DEPs). On the basis of gene ontology (GO) enrichment analysis of DEPs, fold-changes and previous report, cell adhesion-related CD41 (integrin α2b) was selected for further investigation. Our study showed that the CD41 (integrin α2b) was distinctly decreased in ONFH-exos, compared to NOR-exos, and downregulation of CD41 could impair osteogenic differentiation and migration of the MSCs, where CD41-integrin β3-FAK-Akt-Runx2 pathway was involved. Finally, our study further suggested that CD41-affluent NOR-exos could restore the glucocorticoid-induced decline of osteogenic differentiation and migration in MSCs, and prevent GC-induced ONFH-like damage in rat models. Taken together, our study results revealed that in the progress of ONFH, exosomes from the pathological bone brought about the failure of MSCs repairing the necrotic bone for lack of some critical proteins, like integrin CD41, and prompted the progression of experimentally induced ONFH-like status in the rat. CD41 could be considered as the target of early diagnosis and therapy in ONFH.
Identifiants
pubmed: 32341357
doi: 10.1038/s41419-020-2496-y
pii: 10.1038/s41419-020-2496-y
pmc: PMC7184624
doi:
Substances chimiques
Platelet Membrane Glycoprotein IIb
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
293Références
Lei, P. et al. Free vascularized iliac bone flap based on deep circumflex iliac vessels graft for the treatment of osteonecrosis of femoral head. J. Orthop. Surg. Res. 14, 397 (2019).
pubmed: 31779640
pmcid: 6883673
doi: 10.1186/s13018-019-1440-2
Zhao, D., Liu, Y., Ma, C., Gu, G. & Han, D. F. A Mini Review: Stem cell therapy for osteonecrosis of the femoral head and pharmacological aspects. Curr. Pharm. Des. 25, 1099–1104 (2019).
pubmed: 31131747
doi: 10.2174/1381612825666190527092948
pmcid: 31131747
Chughtai, M. et al. An evidence-based guide to the treatment of osteonecrosis of the femoral head. Bone Jt. J. 99-B, 1267–1279 (2017).
doi: 10.1302/0301-620X.99B10.BJJ-2017-0233.R2
Liu, F. et al. An epidemiological study of etiology and clinical characteristics in patients with nontraumatic osteonecrosis of the femoral head. J. Res. Med. Sci. 22, 15 (2017).
pubmed: 28458706
pmcid: 5367210
doi: 10.4103/1735-1995.200273
Lee, Y. J., Cui, Q. & Koo, K. H. Is there a role of pharmacological treatments in the prevention or treatment of osteonecrosis of the femoral head?: a systematic review. J. Bone Metab. 26, 13–18 (2019).
pubmed: 30899719
pmcid: 6416144
doi: 10.11005/jbm.2019.26.1.13
Hernigou, P. et al. Cell therapy versus simultaneous contralateral decompression in symptomatic corticosteroid osteonecrosis: a thirty year follow-up prospective randomized study of one hundred and twenty five adult patients. Int Orthop. 42, 1639–1649 (2018).
pubmed: 29744647
doi: 10.1007/s00264-018-3941-8
pmcid: 29744647
Fang, S., Li, Y. & Chen, P. Osteogenic effect of bone marrow mesenchymal stem cell-derived exosomes on steroid-induced osteonecrosis of the femoral head. Drug Des. Devel. Ther. 13, 45–55 (2019).
pubmed: 30587927
doi: 10.2147/DDDT.S178698
pmcid: 30587927
Xie, Y., Hu, J. Z. & Shi, Z. Y. MiR-181d promotes steroid-induced osteonecrosis of the femoral head by targeting SMAD3 to inhibit osteogenic differentiation of hBMSCs. Eur. Rev. Med. Pharm. Sci. 22, 4053–4062 (2018).
Wu, F. et al. Hypermethylation of Frizzled1 is associated with Wnt/beta-catenin signaling inactivation in mesenchymal stem cells of patients with steroid-associated osteonecrosis. Exp. Mol. Med. 51, 23 (2019).
pmcid: 6391470
Wang, T., Wang, W. & Yin, Z. S. Treatment of osteonecrosis of the femoral head with thorough debridement, bone grafting and bone-marrow mononuclear cells implantation. Eur. J. Orthop. Surg. Traumatol. 24, 197–202 (2014).
pubmed: 23412306
doi: 10.1007/s00590-012-1161-2
pmcid: 23412306
Canas, J. A., Sastre, B., Rodrigo-Munoz, J. M. & Del Pozo, V. Exosomes: a new approach to asthma pathology. Clin. Chim. Acta 495, 139–147 (2019).
pubmed: 30978325
doi: 10.1016/j.cca.2019.04.055
pmcid: 30978325
Stefanius, K. et al. Human pancreatic cancer cell exosomes, but not human normal cell exosomes, act as an initiator in cell transformation. Elife 8, https://doi.org/10.7554/eLife.40226 (2019).
Elahi, F. M., Farwell, D. G., Nolta, J. A. & Anderson, J. D. Preclinical translation of exosomes derived from mesenchymal stem/stromal cells. Stem Cells https://doi.org/10.1002/stem.3061 (2019).
doi: 10.1002/stem.3061
pubmed: 31381842
pmcid: 7004029
Genschmer, K. R. et al. Activated PMN exosomes: pathogenic entities causing matrix destruction and disease in the lung. Cell 176, e115 (2019).
doi: 10.1016/j.cell.2018.12.002
Li, N. et al. Exosome-transmitted miR-25 induced by H. pylori promotes vascular endothelial cell injury by targeting KLF2. Front. Cell Infect. Microbiol 9, 366 (2019).
pubmed: 31750260
pmcid: 6842922
doi: 10.3389/fcimb.2019.00366
Moya-Angeler, J., Gianakos, A. L., Villa, J. C., Ni, A. & Lane, J. M. Current concepts on osteonecrosis of the femoral head. World J. Orthopedics 6, 590–601 (2015).
doi: 10.5312/wjo.v6.i8.590
Huang, L. et al. High levels of GSK-3beta signalling reduce osteogenic differentiation of stem cells in osteonecrosis of femoral head. J. Biochem. 163, 243–251 (2018).
pubmed: 29136173
doi: 10.1093/jb/mvx076
pmcid: 29136173
Hessvik, N. P. & Llorente, A. Current knowledge on exosome biogenesis and release. Cell Mol. Life Sci. 75, 193–208 (2018).
pubmed: 28733901
doi: 10.1007/s00018-017-2595-9
pmcid: 28733901
Hu, N., Feng, C., Jiang, Y., Miao, Q. & Liu, H. Regulative effect of Mir-205 on osteogenic differentiation of bone mesenchymal stem cells (BMSCs): possible role of SATB2/Runx2 and ERK/MAPK pathway. Int J. Mol. Sci. 16, 10491–10506 (2015).
pubmed: 25961955
pmcid: 4463658
doi: 10.3390/ijms160510491
Wang, T. et al. Role of mesenchymal stem cells on differentiation in steroid-induced avascular necrosis of the femoral head. Exp. Ther. Med. 13, 669–675 (2017).
pubmed: 28352349
doi: 10.3892/etm.2016.3991
pmcid: 28352349
Song, M. et al. The effect of electromagnetic fields on the proliferation and the osteogenic or adipogenic differentiation of mesenchymal stem cells modulated by dexamethasone. Bioelectromagnetics 35, 479–490 (2014).
pubmed: 25145543
doi: 10.1002/bem.21867
pmcid: 25145543
Glynn, E. R., Londono, A. S., Zinn, S. A., Hoagland, T. A. & Govoni, K. E. Culture conditions for equine bone marrow mesenchymal stem cells and expression of key transcription factors during their differentiation into osteoblasts. J. Anim. Sci. Biotechnol. 4, 40 (2013).
pubmed: 24169030
pmcid: 3874597
doi: 10.1186/2049-1891-4-40
Awan, B. et al. FGF2 induces migration of human bone marrow stromal cells by increasing core fucosylations on N-glycans of integrins. Stem Cell Rep. 11, 325–333 (2018).
doi: 10.1016/j.stemcr.2018.06.007
Natoli, R. M. et al. Alcohol exposure decreases osteopontin expression during fracture healing and osteopontin-mediated mesenchymal stem cell migration in vitro. J. Orthop. Surg. Res. 13, 101 (2018).
pubmed: 29699560
pmcid: 5921778
doi: 10.1186/s13018-018-0800-7
Shen, G. Y. et al. Plastrum testudinis extracts promote BMSC proliferation and osteogenic differentiation by regulating Let-7f-5p and the TNFR2/PI3K/AKT signaling pathway. Cell Physiol. Biochem. 47, 2307–2318 (2018).
pubmed: 29975930
doi: 10.1159/000491541
pmcid: 29975930
Zhuang, L., Wang, L., Xu, D. & Wang, Z. Anteromedial femoral neck plate with cannulated screws for the treatment of irreducible displaced femoral neck fracture in young patients: a preliminary study. Eur. J. Trauma Emerg. Surg. 45, 995–1002 (2019).
pubmed: 29909465
doi: 10.1007/s00068-018-0972-1
pmcid: 29909465
Yang, F. et al. Vascularized pedicle iliac bone grafts as a hip-preserving surgery for femur head necrosis: a systematic review. J. Orthop. Surg. Res. 14, 270 (2019).
pubmed: 31455329
pmcid: 6710879
doi: 10.1186/s13018-019-1262-2
Lu, Z., Chen, Y., Dunstan, C., Roohani-Esfahani, S. & Zreiqat, H. Priming adipose stem cells with tumor necrosis factor-alpha preconditioning potentiates their exosome efficacy for bone regeneration. Tissue Eng. Part A 23, 1212–1220 (2017).
pubmed: 28346798
doi: 10.1089/ten.tea.2016.0548
pmcid: 28346798
Yin, Y. et al. Upregulating microRNA-410 or downregulating Wnt-11 increases osteoblasts and reduces osteoclasts to alleviate osteonecrosis of the femoral head. Nanoscale Res. Lett. 14, 383 (2019).
pubmed: 31853663
pmcid: 6920280
doi: 10.1186/s11671-019-3221-6
Wu, R. W. et al. S100 calcium binding protein A9 represses angiogenic activity and aggravates osteonecrosis of the femoral head. Int. J. Mol. Sci. 20, https://doi.org/10.3390/ijms20225786 (2019).
Yu, H. et al. Icariin promotes angiogenesis in glucocorticoid-induced osteonecrosis of femoral heads: In vitro and in vivo studies. J. Cell Mol. Med. 23, 7320–7330 (2019).
pubmed: 31507078
pmcid: 6815836
doi: 10.1111/jcmm.14589
Cui, L. et al. Multicentric epidemiologic study on six thousand three hundred and ninety five cases of femoral head osteonecrosis in China. Int. Orthop. 40, 267–276 (2016).
pubmed: 26660727
doi: 10.1007/s00264-015-3061-7
pmcid: 26660727
Xie, Y. et al. Involvement of serum-derived exosomes of elderly patients with bone loss in failure of bone remodeling via alteration of exosomal bone-related proteins. Aging Cell 17, e12758 (2018).
pubmed: 29603567
pmcid: 5946082
doi: 10.1111/acel.12758
Li, H. et al. Exosomes secreted from mutant-HIF-1alpha-modified bone-marrow-derived mesenchymal stem cells attenuate early steroid-induced avascular necrosis of femoral head in rabbit. Cell Biol. Int. 41, 1379–1390 (2017).
pubmed: 28877384
doi: 10.1002/cbin.10869
pmcid: 28877384
Guo, S. C. et al. Exosomes from human synovial-derived mesenchymal stem cells prevent glucocorticoid-induced osteonecrosis of the femoral head in the rat. Int. J. Biol. Sci. 12, 1262–1272 (2016).
pubmed: 27766040
pmcid: 5069447
doi: 10.7150/ijbs.16150
Gao, M. et al. Exosomes-the enigmatic regulators of bone homeostasis. Bone Res. 6, 36 (2018).
pubmed: 30534458
pmcid: 6286319
doi: 10.1038/s41413-018-0039-2
Xu, M. & Peng, D. Mesenchymal stem cells cultured on tantalum used in early-stage avascular necrosis of the femoral head. Med. Hypotheses 76, 199–200 (2011).
pubmed: 20970260
doi: 10.1016/j.mehy.2010.09.028
Fahmy-Garcia, S. et al. Follistatin effects in migration, vascularization, and osteogenesis in vitro and bone repair in vivo. Front. Bioeng. Biotechnol. 7, 38 (2019).
pubmed: 30881954
pmcid: 6405513
doi: 10.3389/fbioe.2019.00038
Li, X. et al. MiR-9-5p promotes MSC migration by activating beta-catenin signaling pathway. Am. J. Physiol. Cell Physiol. 313, C80–C93 (2017).
pubmed: 28424168
doi: 10.1152/ajpcell.00232.2016
Bohm, A. M. et al. Activation of skeletal stem and progenitor cells for bone regeneration is driven by PDGFRbeta signaling. Dev. Cell 51, 236–254 e212 (2019).
pubmed: 31543445
doi: 10.1016/j.devcel.2019.08.013
pmcid: 31543445
Qiu, P. et al. Periosteal matrix-derived hydrogel promotes bone repair through an early immune regulation coupled with enhanced angio- and osteogenesis. Biomaterials 227, 119552 (2020).
pubmed: 31670079
doi: 10.1016/j.biomaterials.2019.119552
pmcid: 31670079
Olivares-Navarrete, R. et al. Integrin alpha2beta1 plays a critical role in osteoblast response to micron-scale surface structure and surface energy of titanium substrates. Proc. Natl Acad. Sci. USA 105, 15767–15772 (2008).
pubmed: 18843104
doi: 10.1073/pnas.0805420105
pmcid: 18843104
Moon, Y. J. et al. Osterix regulates corticalization for longitudinal bone growth via integrin beta3 expression. Exp. Mol. Med. 50, 80 (2018).
Gekas, C. & Graf, T. CD41 expression marks myeloid-biased adult hematopoietic stem cells and increases with age. Blood 121, 4463–4472 (2013).
pubmed: 23564910
doi: 10.1182/blood-2012-09-457929
pmcid: 23564910
Wang, X. et al. Exosomes influence the behavior of human mesenchymal stem cells on titanium surfaces. Biomaterials 230, 119571 (2020).
pubmed: 31753474
doi: 10.1016/j.biomaterials.2019.119571
pmcid: 31753474
Luo, K. et al. Multiple integrin ligands provide a highly adhesive and osteoinductive surface that improves selective cell retention technology. Acta Biomater. 85, 106–116 (2019).
pubmed: 30557698
doi: 10.1016/j.actbio.2018.12.018
pmcid: 30557698
Zhang, J. et al. Exosomes/tricalcium phosphate combination scaffolds can enhance bone regeneration by activating the PI3K/Akt signaling pathway. Stem Cell Res. Ther. 7, 136 (2016).
pubmed: 27650895
pmcid: 5028974
doi: 10.1186/s13287-016-0391-3
Li, H. et al. miR-216a rescues dexamethasone suppression of osteogenesis, promotes osteoblast differentiation and enhances bone formation, by regulating c-Cbl-mediated PI3K/AKT pathway. Cell Death Differ. 22, 1935–1945 (2015).
pubmed: 26206089
pmcid: 4816120
doi: 10.1038/cdd.2015.99
Thiagarajan, L., Abu-Awwad, H. A. M. & Dixon, J. E. Osteogenic programming of human mesenchymal stem cells with highly efficient intracellular delivery of RUNX2. Stem Cells Transl. Med. 6, 2146–2159 (2017).
pubmed: 29090533
pmcid: 5702512
doi: 10.1002/sctm.17-0137
Jeppesen, D. K. et al. Comparative analysis of discrete exosome fractions obtained by differential centrifugation. J. Extracell. Vesicles 3, 25011 (2014).
pubmed: 25396408
doi: 10.3402/jev.v3.25011
pmcid: 25396408
Zarovni, N. et al. Integrated isolation and quantitative analysis of exosome shuttled proteins and nucleic acids using immunocapture approaches. Methods 87, 46–58 (2015).
pubmed: 26044649
doi: 10.1016/j.ymeth.2015.05.028
pmcid: 26044649
Vella, L. J. et al. A rigorous method to enrich for exosomes from brain tissue. J. Extracell. Vesicles 6, 1348885 (2017).
pubmed: 28804598
pmcid: 5533148
doi: 10.1080/20013078.2017.1348885
Li, P., Kaslan, M., Lee, S. H., Yao, J. & Gao, Z. Progress in exosome isolation techniques. Theranostics 7, 789–804 (2017).
pubmed: 28255367
pmcid: 5327650
doi: 10.7150/thno.18133
Petho, A., Chen, Y. & George, A. Exosomes in extracellular matrix bone biology. Curr. Osteoporos. Rep. 16, 58–64 (2018).
pubmed: 29372401
pmcid: 5812795
doi: 10.1007/s11914-018-0419-y
Ramirez, M. I. et al. Technical challenges of working with extracellular vesicles. Nanoscale 10, 881–906 (2018).
pubmed: 29265147
doi: 10.1039/C7NR08360B
pmcid: 29265147
Zhang, P. et al. Identification of plasma biomarkers for diffuse axonal injury in rats by iTRAQ-coupled LC-MS/MS and bioinformatics analysis. Brain Res. Bull. 142, 224–232 (2018).
pubmed: 30077728
doi: 10.1016/j.brainresbull.2018.07.015
pmcid: 30077728
Ma, J. et al. iProX: an integrated proteome resource. Nucleic Acids Res. 47, D1211–D1217 (2019).
pubmed: 30252093
doi: 10.1093/nar/gky869
pmcid: 30252093