Gas-powered extracellular vesicles promote bone regeneration

Lexie Shannon Holliday , John K. Neubert , Xianrui Yang

Extracellular Vesicles and Circulating Nucleic Acids ›› 2025, Vol. 6 ›› Issue (1) : 158 -65.

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Extracellular Vesicles and Circulating Nucleic Acids ›› 2025, Vol. 6 ›› Issue (1) :158 -65. DOI: 10.20517/evcna.2024.91
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Gas-powered extracellular vesicles promote bone regeneration

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Abstract

The signaling gas hydrogen sulfide (H2S) has recently been implicated in the regulation of bone remodeling and the maintenance of periodontal health. Exploring the underlying mechanisms for this regulation holds promise for the development of new treatment strategies to block bone resorption and stimulate bone regeneration. A recent study by Zhou et al. (Bioactive Materials, 2024) showed that treatment with H2S stimulated changes in the extracellular vesicles (EVs) released by M2 macrophages, enhancing their capacity to promote the osteogenic differentiation of mesenchymal stem cells in vitro. The H2S-stimulated EVs, given together with mesenchymal stem cells (MSCs), also promoted bone regeneration in vivo in a mouse calvarial critical-size defect model. This activity was linked to augmented expression of moesin, a membrane-cytoskeletal linkage protein, which was found at increased levels in EVs from cells stimulated by H2S. The study identifies a new strategy for generating EVs that are pro-osteogenic. It also uncovers a surprising role for moesin in stimulating osteogenesis in MSCs.

Keywords

Osteogenesis / exosomes / hydrogen sulfide / moesin / Wnt/β-catenin / macrophage / osteoblast

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Lexie Shannon Holliday, John K. Neubert, Xianrui Yang. Gas-powered extracellular vesicles promote bone regeneration. Extracellular Vesicles and Circulating Nucleic Acids, 2025, 6(1): 158-65 DOI:10.20517/evcna.2024.91

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References

[1]

Abe K.The possible role of hydrogen sulfide as an endogenous neuromodulator.J Neurosci1996;16:1066-71 PMCID:PMC6578817

[2]

Cirino G,Papapetropoulos A.Physiological roles of hydrogen sulfide in mammalian cells, tissues, and organs.Physiol Rev2023;103:31-276

[3]

Oza PP.The triple crown: NO, CO, and H2S in cancer cell biology.Pharmacol Ther2023;249:108502 PMCID:PMC10529678

[4]

Yang G,Jiang B.H2S as a physiologic vasorelaxant: hypertension in mice with deletion of cystathionine gamma-lyase.Science2008;322:587-90 PMCID:PMC2749494

[5]

Jiang M,Yan X.A novel rhein derivative modulates bone formation and resorption and ameliorates estrogen-dependent bone loss.J Bone Miner Res2019;34:361-74

[6]

Zhang CH,Meng Y.Hydrogen sulfide and its donors: novel antitumor and antimetastatic agents for liver cancer.Cell Signal2023;106:110628

[7]

Tang G,Liang W.Direct stimulation of K(ATP) channels by exogenous and endogenous hydrogen sulfide in vascular smooth muscle cells.Mol Pharmacol2005;68:1757-64

[8]

Yang W,Jia X,Wang R.Activation of KATP channels by H2S in rat insulin-secreting cells and the underlying mechanisms.J Physiol2005;569:519-31 PMCID:PMC1464240

[9]

Kida M,Yoshimoto T.Hydrogen sulfide increases nitric oxide production with calcium-dependent activation of endothelial nitric oxide synthase in endothelial cells.Eur J Pharm Sci2013;48:211-5

[10]

Makarenko VV,Yuan G.CaV3.2 T-type Ca2+ channels in H2S-mediated hypoxic response of the carotid body.Am J Physiol Cell Physiol2015;308:C146-54 PMCID:PMC4297770

[11]

Yu M,Wang B.Exogenous H2S induces Hrd1 S-sulfhydration and prevents CD36 translocation via VAMP3 ubiquitylation in diabetic hearts.Aging Dis2020;11:286-300 PMCID:PMC7069459

[12]

Leslie M.Inflammation’s stop signals.Science2015;347:18-21

[13]

Ye S,Liu N.Gases and gas-releasing materials for the treatment of chronic diabetic wounds.Biomater Sci2024;12:3273-92

[14]

Cao H,Zhang J.Hydrogen sulfide protects against bleomycin-induced pulmonary fibrosis in rats by inhibiting NF-κB expression and regulating Th1/Th2 balance.Toxicol Lett2014;224:387-94

[15]

Datzmann T,McCook O,Radermacher P.H2S as a therapeutic adjuvant against COVID-19: why and how?.Shock2021;56:865-7 PMCID:PMC8518209

[16]

Zhou YK,Zhu ZL.M2 exosomes modified by hydrogen sulfide promoted bone regeneration by moesin mediated endocytosis.Bioact Mater2023;31:192-205 PMCID:PMC10429289

[17]

Welsh JA, Goberdhan DCI, O'Driscoll L, et al; MISEV Consortium. Minimal information for studies of extracellular vesicles (MISEV2023): from basic to advanced approaches. J Extracell Vesicles. 2024;13:e12404. PMCID:PMC11082720

[18]

Horibe K,Nakamura H.M2-like macrophage infiltration and transforming growth factor-β secretion during socket healing process in mice.Arch Oral Biol2021;123:105042

[19]

Schlundt C,Bucher CH,Duda GN.The multifaceted roles of macrophages in bone regeneration: a story of polarization, activation and time.Acta Biomater2021;133:46-57

[20]

Kong L,Smith W.Macrophages in bone homeostasis.Curr Stem Cell Res Ther2019;14:474-81

[21]

Zhang C,Yang YT,Li Y.[Role of M2 macrophage exosomes in osteogenic differentiation of mouse bone marrow mesenchymal stem cells under high-glucose and high-insulin].Sichuan Da Xue Xue Bao Yi Xue Ban2022;53:63-70 PMCID:PMC10408854

[22]

Liu K,Lv ZY.Macrophage-derived exosomes promote bone mesenchymal stem cells towards osteoblastic fate through microRNA-21a-5p.Front Bioeng Biotechnol2021;9:801432 PMCID:PMC8766741

[23]

Bin-Bin Z,Chao L.M2 macrophagy-derived exosomal miRNA-26a-5p induces osteogenic differentiation of bone mesenchymal stem cells.J Orthop Surg Res2022;17:137 PMCID:PMC8895825

[24]

Chen X,Yang L.Exosomes derived from reparative M2-like macrophages prevent bone loss in murine periodontitis models via IL-10 mRNA.J Nanobiotechnology2022;20:110 PMCID:PMC8898524

[25]

Li Z,Li S.Exosomes derived from M2 macrophages facilitate osteogenesis and reduce adipogenesis of BMSCs.Front Endocrinol2021;12:680328 PMCID:PMC8290518

[26]

Kang M,Lu Y.Bone regeneration is mediated by macrophage extracellular vesicles.Bone2020;141:115627 PMCID:PMC8107826

[27]

Sauvanet C,Pelaseyed T.Structure, regulation, and functional diversity of microvilli on the apical domain of epithelial cells.Annu Rev Cell Dev Biol2015;31:593-621

[28]

Ogihara T,Kamioka H.Physiological roles of ERM proteins and transcriptional regulators in supporting membrane expression of efflux transporters as factors of drug resistance in cancer.Cancers2020;12:3352 PMCID:PMC7696277

[29]

Bajusz C,Abonyi C.The nuclear activity of the actin-binding Moesin protein is necessary for gene expression in Drosophila.FEBS J2021;288:4812-32

[30]

Frame MC,Serrels B,Eck MJ.The FERM domain: organizing the structure and function of FAK.Nat Rev Mol Cell Biol2010;11:802-14

[31]

Rody WJ Jr,Emory-Carter AK.The proteome of extracellular vesicles released by clastic cells differs based on their substrate.PLoS One2019;14:e0219602 PMCID:PMC6619814

[32]

Holliday LS,Rody WJ Jr.Actin and actin-associated proteins in extracellular vesicles shed by osteoclasts.Int J Mol Sci2019;21:158 PMCID:PMC6981389

[33]

Cruciat CM,Acebron SP.Requirement of prorenin receptor and vacuolar H+-ATPase-mediated acidification for Wnt signaling.Science2010;327:459-63

[34]

Martin-Orozco E,Ortiz-Parra I.WNT signaling in tumors: the way to evade drugs and immunity.Front Immunol2019;10:2854 PMCID:PMC6934036

[35]

Orian-Rousseau V.CD44 acts as a signaling platform controlling tumor progression and metastasis.Front Immunol2015;6:154 PMCID:PMC4389564

[36]

Kleinman HK,Goldstein AL.Thymosin β4 and the anti-fibrotic switch.Int Immunopharmacol2023;115:109628

[37]

Chu X,Li T.Hydrogen sulfide-modified extracellular vesicles from mesenchymal stem cells for treatment of hypoxic-ischemic brain injury.J Control Release2020;328:13-27

[38]

Holliday LS PS.RANKL and RANK in extracellular vesicles: surprising new players in bone remodeling.Extracellular Vesicles Circ Nucl Acids2021;2:18-28. PMCID:PMC8112638

[39]

Datta A,McGee L.High-throughput screening identified selective inhibitors of exosome biogenesis and secretion: a drug repurposing strategy for advanced cancer.Sci Rep2018;8:8161 PMCID:PMC5970137

[40]

Du W,Zhang S.Enhanced proangiogenic potential of mesenchymal stem cell-derived exosomes stimulated by a nitric oxide releasing polymer.Biomaterials2017;133:70-81

[41]

Lu C,Hua Y.Cystathionine gamma lyase aggravates orthodontic root resorption in mice.Ann Transl Med2019;7:787 PMCID:PMC6989964

[42]

Liu F,He D.Force-induced H2S by PDLSCs modifies osteoclastic activity during tooth movement.J Dent Res2017;96:694-702

[43]

Song D,Cheng T.Cystathionine γ-lyase contributes to exacerbation of periodontal destruction in experimental periodontitis under hyperglycemia.J Periodontol2024;Epub ahead of print:

[44]

Planells-Cases R,Messeguer A,Ferrer-Montiel A.Small molecules targeting the NMDA receptor complex as drugs for neuropathic pain.Mini Rev Med Chem2003;3:749-56

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