Hypoxia preconditioned DPSC-derived exosomes regulate angiogenesis via transferring LOXL2

Li, Baoyu; Liang, Ailin; Zhou, Yanling; Huang, Yihua; Liao, Chenxi; Zhang, Xufang; Gong, Qimei

doi:10.1016/j.yexcr.2023.113543

Cited by 9 publications

(6 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although we focused on succinate and SUCNR1 in the present study, the regulatory roles of other signals should also be further investigated. For example, hypoxic DPSCs release exosomes to enhance angiogenesis 47 . Small extracellular vesicles released from hypoxic DPSCs inhibit inflammatory osteolysis by reducing macrophage polarization and osteoclastogenesis 48 .…”

Section: Discussionmentioning

confidence: 99%

Hypoxic dental pulp stem cells-released succinate promotes osteoclastogenesis and root resorption

Yang,

Wang,

Yang

et al. 2024

Int. J. Med. Sci.

View full text Add to dashboard Cite

Introduction: Clinical studies have shown that endodontically-treated nonvital teeth exhibit less root resorption during orthodontic tooth movement. The purpose of this study was to explore whether hypoxic dental pulp stem cells (DPSCs) can promote osteoclastogenesis in orthodontically induced inflammatory root resorption (OIIRR). Methods: Succinate in the supernatant of DPSCs under normal and hypoxic conditions was measured by a succinic acid assay kit. The culture supernatant of hypoxia-treated DPSCs was used as conditioned medium (Hypo-CM). Bone marrow-derived macrophages (BMDMs) from succinate receptor 1 (SUCNR1)-knockout or wild-type mice were cultured with conditioned medium (CM), exogenous succinate or a specific inhibitor of SUCNR1 (4c). Tartrate-resistant acid phosphatase (TRAP) staining, Transwell assays, qPCR, Western blotting, and resorption assays were used to evaluate osteoclastogenesis-related changes. Results: The concentration of succinate reached a maximal concentration at 6 h in the supernatant of hypoxia-treated DPSCs. Hypo-CM-treated macrophages were polarized to M1 proinflammatory macrophages. Hypo-CM treatment significantly increased the formation and differentiation of osteoclasts and increased the expression of osteoclastogenesis-related genes, and this effect was inhibited by the specific succinate inhibitor 4c. Succinate promoted chemotaxis and polarization of M1-type macrophages with increased expression of osteoclast generation-related genes. SUCNR1 knockout decreased macrophage migration, M1 macrophage polarization, differentiation and maturation of osteoclasts, as shown by TRAP and NFATc1 expression and cementum resorption. Conclusions: Hypoxic DPSC-derived succinate may promote osteoclast differentiation and root resorption. The regulation of the succinate-SUCNR1 axis may contribute to the reduction in the OIIRR.

show abstract

Section: Discussionmentioning

confidence: 99%

Hypoxic dental pulp stem cells-released succinate promotes osteoclastogenesis and root resorption

Yang,

Wang,

Yang

et al. 2024

Int. J. Med. Sci.

View full text Add to dashboard Cite

show abstract

“…Also, these sEVs could facilitate HUVECs proliferation, migration and tube formation with upregulation of LOXL2, and rescue the inhibition of tube formation caused by LOXL2 silencing in HUVECs [49]. Their further study showed that LOXL2 silencing in hypoxic DPSC-derived sEVs partially reversed the promotion of HUVEC migration and formation, and inhibited the expression of angiogenesisassociated genes, indicating that LOXL2 plays an important role in mediating the angiogenic effects of hypoxic DPSCderived sEVs [62].…”

Section: Hif-1α Signalingmentioning

confidence: 95%

“…Emerging evidence suggests the existence of a regulatory loop between LOXL2 and HIF-1α, with hypoxia-induced upregulation of LOXL2 being directly mediated by HIF-1α, and LOXL2 in turn regulating the HIF-1α/VEGF signaling pathways [59][60][61]. It has been reported that LOXL2 silencing in DPSCs inhibited their proliferation and migration [62]. Additionally, Li et al found that LOXL2 was upregulated in both hypoxia conditioned DPSCs and their secreted sEVs [49].…”

Section: Hif-1α Signalingmentioning

confidence: 99%

Role of Hypoxia in Mesenchymal Stem Cells from Dental Pulp: Influence, Mechanism and Application

2024

Cell Biochem Biophys

View full text Add to dashboard Cite

Mesenchymal stem cells (MSCs) from dental pulp (DP-MSCs), which include dental pulp stem cells (DPSCs) isolated from permanent teeth and stem cells from human exfoliated deciduous teeth (SHED), have emerged as highly promising cell sources for tissue regeneration, due to their high proliferative rate, multi-lineage differentiation capability and non-invasive accessibility. DP-MSCs also exert extensive paracrine effects through the release of extracellular vesicles (EVs) and multiple trophic factors. To be noted, the microenvironment, commonly referred to as the stem cell niche, plays a crucial role in shaping the functionality and therapeutic effects of DP-MSCs, within which hypoxia has garnered considerable attention. Extensive research has demonstrated that hypoxic conditions profoundly impact DP-MSCs. Specifically, hypoxia promotes DP-MSC proliferation, survival, stemness, migration, and pro-angiogenic potential while modulating their multi-lineage differentiation capacity. Furthermore, hypoxia stimulates the paracrine activities of DP-MSCs, leading to an increased production of EVs and soluble factors. Considering these findings, hypoxia preconditioning has emerged as a promising approach to enhance the therapeutic potential of DP-MSCs. In this comprehensive review, we provide a systematic overview of the influence of hypoxia on DP-MSCs, shedding light on the underlying mechanisms involved. Moreover, we also discuss the potential applications of hypoxia-preconditioned DP-MSCs or their secretome in tissue regeneration. Additionally, we delve into the methodologies employed to simulate hypoxic environments. This review aims to promote a comprehensive and systematic understanding of the hypoxia-induced effects on DP-MSCs and facilitate the refinement of regenerative therapeutic strategies based on DP-MSCs. Graphical Abstract

show abstract

“… 156 LPS also promotes angiogenesis via DPSC-derived exosomes, 157 – 159 which simultaneously could be enhanced by hypoxia with higher level of lysyl oxidase-like 2 (LOXL2). 160 , 161 Compared with a normal status, DPSCs under odontogenic differentiation condition secrete more effective exosomes, for instance, the levels of miR-27a-5p are elevated, which induces DPSC differentiation. 154 , 162 Furthermore, the evidence suggested that younger donors of DPSCs gave better performance to exosomal ability in pulp regeneration, 163 as exosomal miR-26a secreted by aggregating stem cells from deciduous teeth (SHED) strongly promotes the angiogenesis of HUVECs in pulp tissue through TGF-β/Smad2/3 signaling.…”

Section: Exosomes In Targeted Therapy For Oral Diseasesmentioning

confidence: 99%

Emerging roles of exosomes in oral diseases progression

Wang,

Jing,

Zhou

et al. 2024

Int J Oral Sci

View full text Add to dashboard Cite

Oral diseases, such as periodontitis, salivary gland diseases, and oral cancers, significantly challenge health conditions due to their detrimental effects on patient’s digestive functions, pronunciation, and esthetic demands. Delayed diagnosis and non-targeted treatment profoundly influence patients’ prognosis and quality of life. The exploration of innovative approaches for early detection and precise treatment represents a promising frontier in oral medicine. Exosomes, which are characterized as nanometer-sized extracellular vesicles, are secreted by virtually all types of cells. As the research continues, the complex roles of these intracellular-derived extracellular vesicles in biological processes have gradually unfolded. Exosomes have attracted attention as valuable diagnostic and therapeutic tools for their ability to transfer abundant biological cargos and their intricate involvement in multiple cellular functions. In this review, we provide an overview of the recent applications of exosomes within the field of oral diseases, focusing on inflammation-related bone diseases and oral squamous cell carcinomas. We characterize the exosome alterations and demonstrate their potential applications as biomarkers for early diagnosis, highlighting their roles as indicators in multiple oral diseases. We also summarize the promising applications of exosomes in targeted therapy and proposed future directions for the use of exosomes in clinical treatment.

show abstract

Hypoxia preconditioned DPSC-derived exosomes regulate angiogenesis via transferring LOXL2

Cited by 9 publications

References 40 publications

Hypoxic dental pulp stem cells-released succinate promotes osteoclastogenesis and root resorption

Hypoxic dental pulp stem cells-released succinate promotes osteoclastogenesis and root resorption

Role of Hypoxia in Mesenchymal Stem Cells from Dental Pulp: Influence, Mechanism and Application

Emerging roles of exosomes in oral diseases progression

Contact Info

Product

Resources

About