Immunomodulatory Effects of MSCs in Bone Healing

Medhat, Dalia; Rodrı́guez, Clara I.; Infante, Arantza

doi:10.3390/ijms20215467

Cited by 72 publications

(57 citation statements)

References 112 publications

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“…Researchers have made an initial breakthrough in the molecular mechanism of osteoclastogenesis with coculture systems comprising BMMs and BMSCs or T cells . More and more inflammatory and chemotactic mediators have been confirmed to launch the activation of BMSCs leading to bone remodelling, such as TNF‐α, IL‐1, IL‐6, IL‐17 and IL‐22 . In our study, we found that BMSC CM notably increased RANKL‐induced osteoclastogenesis and bone resorption, which was upregulated or downregulated by IL‐20 in a dose‐dependent manner.…”

Section: Discussionsupporting

confidence: 48%

Interleukin‐20 differentially regulates bone mesenchymal stem cell activities in RANKL‐induced osteoclastogenesis through the OPG/RANKL/RANK axis and the NF‐κB, MAPK and AKT signalling pathways

Meng

Cheng

et al. 2020

Scand J Immunol

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The immune and skeletal systems share common mechanisms, and the crosstalk between the two has been termed osteoimmunology. Osteoimmunology mainly focuses on diseases between the immune and bone systems including bone loss diseases, and imbalances in osteoimmune regulation affect skeletal homeostasis between osteoclasts and osteoblasts. The immune mediator interleukin‐20 (IL‐20), a member of the IL‐10 family, enhances inflammation, chemotaxis and angiogenesis in diseases related to bone loss. However, it is unclear how IL‐20 regulates the balance between osteoclastogenesis and osteoblastogenesis; therefore, we explored the mechanisms by which IL‐20 affects bone mesenchymal stem cells (BMSCs) in osteoclastogenesis in primary cells during differentiation, proliferation, apoptosis and signalling. We initially found that IL‐20 differentially regulated preosteoclast proliferation and apoptosis; BMSC‐conditioned medium (CM) significantly enhanced osteoclast formation and bone resorption, which was dose‐dependently regulated by IL‐20; IL‐20 inhibited OPG expression and promoted M‐CSF, RANKL and RANKL/OPG expression; and IL‐20 differentially regulated the expression of osteoclast‐specific gene and transcription factors through the OPG/RANKL/RANK axis and the NF‐kB, MAPK and AKT pathways. Therefore, IL‐20 differentially regulates BMSCs in osteoclastogenesis and exerts its function by activating the OPG/RANKL/RANK axis and the NF‐κB, MAPK and AKT pathways, which make targeting IL‐20 a promising direction for targeted regulation in diseases related to bone loss.

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Section: Discussionsupporting

confidence: 48%

Interleukin‐20 differentially regulates bone mesenchymal stem cell activities in RANKL‐induced osteoclastogenesis through the OPG/RANKL/RANK axis and the NF‐κB, MAPK and AKT signalling pathways

Meng

Cheng

et al. 2020

Scand J Immunol

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“…MSCs undergo the multi-step process of osteogenesis in response to different cues (of both biochemical and mechanical nature) coming mainly from the surrounding ECM [ 22 , 23 ]. Moreover, in the bone healing process, inflammatory mediators activate and mobilize tissue-resident, endogenous MSCs which migrate from their niche to the damaged site in order to facilitate bone tissue regeneration [ 24 ]. To achieve both migration and osteogenic differentiation, MSCs must reorganize their nuclear lamina shape and/or composition, with lamin A orchestrating this process.…”

Section: Introductionmentioning

confidence: 99%

Crucial Role of Lamin A/C in the Migration and Differentiation of MSCs in Bone

Alcorta-Sevillano

Macías

Rodrı́guez

et al. 2020

Cells

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Lamin A/C, intermediate filament proteins from the nuclear lamina encoded by the LMNA gene, play a central role in mediating the mechanosignaling of cytoskeletal forces into nucleus. In fact, this mechanotransduction process is essential to ensure the proper functioning of other tasks also mediated by lamin A/C: the structural support of the nucleus and the regulation of gene expression. In this way, lamin A/C is fundamental for the migration and differentiation of mesenchymal stem cells (MSCs), the progenitors of osteoblasts, thus affecting bone homeostasis. Bone formation is a complex process regulated by chemical and mechanical cues, coming from the surrounding extracellular matrix. MSCs respond to signals modulating the expression levels of lamin A/C, and therefore, adapting their nuclear shape and stiffness. To promote cell migration, MSCs need soft nuclei with low lamin A content. Conversely, during osteogenic differentiation, lamin A/C levels are known to be increased. Several LMNA mutations present a negative impact in the migration and osteogenesis of MSCs, affecting bone tissue homeostasis and leading to pathological conditions. This review aims to describe these concepts by discussing the latest state-of-the-art in this exciting area, focusing on the relationship between lamin A/C in MSCs’ function and bone tissue from both, health and pathological points of view.

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“…MSCs have been shown to possess immunoregulatory abilities [176], being capable of interacting with cells of both adaptive and innate response: B cells, T cells, dendritic cells (DCs), natural killer (NK) cells, neutrophils and macrophages [177]. These immunomodulation relies on cell-cell contact in collaboration with the secretion of soluble immune factors [178] namely; TGFβ1, hepatocyte growth factor (HGF), indoleamine-2, 3-dioxygenase, prostaglandin E2 (PGE2), interleukin-10 (IL-10), HLA-G5 and galectins.…”

Section: Mscs Immunoregulatory Capabilitiesmentioning

confidence: 99%

Osteoporosis and the Potential of Cell-Based Therapeutic Strategies

Macías

Alcorta-Sevillano

Rodrı́guez

et al. 2020

IJMS

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Osteoporosis, the most common chronic metabolic bone disease, is characterized by low bone mass and increased bone fragility. Nowadays more than 200 million individuals are suffering from osteoporosis and still the number of affected people is dramatically increasing due to an aging population and longer life, representing a major public health problem. Current osteoporosis treatments are mainly designed to decrease bone resorption, presenting serious adverse effects that limit their safety for long-term use. Numerous studies with mesenchymal stem cells (MSCs) have helped to increase the knowledge regarding the mechanisms that underlie the progression of osteoporosis. Emerging clinical and molecular evidence suggests that inflammation exerts a significant influence on bone turnover, thereby on osteoporosis. In this regard, MSCs have proven to possess broad immunoregulatory capabilities, modulating both adaptive and innate immunity. Here, we will discuss the role that MSCs play in the etiopathology of osteoporosis and their potential use for the treatment of this disease.

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Immunomodulatory Effects of MSCs in Bone Healing

Cited by 72 publications

References 112 publications

Interleukin‐20 differentially regulates bone mesenchymal stem cell activities in RANKL‐induced osteoclastogenesis through the OPG/RANKL/RANK axis and the NF‐κB, MAPK and AKT signalling pathways

Interleukin‐20 differentially regulates bone mesenchymal stem cell activities in RANKL‐induced osteoclastogenesis through the OPG/RANKL/RANK axis and the NF‐κB, MAPK and AKT signalling pathways

Crucial Role of Lamin A/C in the Migration and Differentiation of MSCs in Bone

Osteoporosis and the Potential of Cell-Based Therapeutic Strategies

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