The miR151 and miR5100 Transfected Bone Marrow Stromal Cells Increase Myoblast Fusion in IGFBP2 Dependent Manner

Mierzejewski, Bartosz; Michalska, Zuzanna; Jackowski, Daniel; Stremińska, Władysława; Jańczyk-Ilach, Katarzyna; Koblowska, Marta; Iwanicka-Nowicka, Roksana; Gromadka, Agnieszka; Ciemerych, Maria A.; Brzóska, Edyta

doi:10.1007/s12015-022-10350-y

Cited by 3 publications

(1 citation statement)

References 62 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, it was shown that they can fuse with myoblasts and incorporate into newly formed myofibers, although to a very limited extent [ 33 ]. In mice, it was also shown that the myogenic potential of BMSCs, defined as the ability to convert into myogenic cells, can be promoted by overexpression of genes encoding NICD (Notch Intracellular Domain), β-CATENIN, PAX3 or miRNAs involved in muscle regeneration [ 34 , 35 ]. Despite the limited naïve myogenic potential, BMSCs are still considered in terms of therapy for dysfunctional muscles due to their other properties, that is as immunomodulatory agents.…”

Section: Discussionmentioning

confidence: 99%

Comparison of Muscle Regeneration after BMSC-Conditioned Medium, Syngeneic, or Allogeneic BMSC Injection

Świerczek-Lasek

Tolak

Bijoch

et al. 2022

Cells

Self Cite

View full text Add to dashboard Cite

For many years optimal treatment for dysfunctional skeletal muscle characterized, for example, by impaired or limited regeneration, has been searched. Among the crucial factors enabling its development is finding the appropriate source of cells, which could participate in tissue reconstruction or serve as an immunomodulating agent (limiting immune response as well as fibrosis, that is, connective tissue formation), after transplantation to regenerating muscles. MSCs, including those derived from bone marrow, are considered for such applications in terms of their immunomodulatory properties, as their naive myogenic potential is rather limited. Injection of autologous (syngeneic) or allogeneic BMSCs has been or is currently being tested and compared in many potential clinical treatments. In the present study, we verified which approach, that is, the transplantation of either syngeneic or allogeneic BMSCs or the injection of BMSC-conditioned medium, would be the most beneficial for skeletal muscle regeneration. To properly assess the influence of the tested treatments on the inflammation, the experiments were carried out using immunocompetent mice, which allowed us to observe immune response. Combined analysis of muscle histology, immune cell infiltration, and levels of selected chemokines, cytokines, and growth factors important for muscle regeneration, showed that muscle injection with BMSC-conditioned medium is the most beneficial strategy, as it resulted in reduced inflammation and fibrosis development, together with enhanced new fiber formation, which may be related to, i.e., elevated level of IGF-1. In contrast, transplantation of allogeneic BMSCs to injured muscles resulted in a visible increase in the immune response, which hindered regeneration by promoting connective tissue formation. In comparison, syngeneic BMSC injection, although not detrimental to muscle regeneration, did not result in such significant improvement as CM injection.

show abstract

Section: Discussionmentioning

confidence: 99%

Comparison of Muscle Regeneration after BMSC-Conditioned Medium, Syngeneic, or Allogeneic BMSC Injection

Świerczek-Lasek

Tolak

Bijoch

et al. 2022

Cells

Self Cite

View full text Add to dashboard Cite

show abstract

Evolutionary analysis and functional characterization reveal the role of the insulin-like growth factor system in a diversified selection of chickens (Gallus gallus)

Guo¹,

Zhang²,

Geng³

et al. 2023

Poultry Science

View full text Add to dashboard Cite

The miR-6240 target gene Igf2bp3 promotes myoblast fusion by enhancing myomaker mRNA stability

Huang,

Wang,

Fan

et al. 2024

Cell Mol Biol Lett

View full text Add to dashboard Cite

Background Myoblast fusion plays a crucial role in myogenesis. Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) functions as an RNA N6-methyladenosine reader and exerts important roles in various biological processes. While our prior study suggested Igf2bp3 contributes to myogenesis, its molecular regulatory mechanism is largely unclear. Methods Real-time quantitative polymerase chain reaction (RT-qPCR) and western blot were used for gene expression analysis. siRNA and CRISPRi technologies were conducted to knockdown the expression of Igf2bp3. CRISPR/Cas9 technology was performed to knockout Igf2bp3. The Igf2bp3 overexpression vector was designed using the pcDNA3.1(+) vector. Immunofluorescence detection was employed for subcellular localization and cell differentiation analysis. Cell Counting Kit-8 (CCK-8) and 5-ethynyl-2′-deoxyuridine (EdU) assays were conducted for cell proliferation and fusion detection. The dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were utilized for regulatory mechanism analysis of Igf2bp3. Results The overexpression of Igf2bp3 enhances myoblast fusion while knockdown of Igf2bp3 blocks the formation of myotubes. miR-6240 promotes myoblast proliferation while preventing myoblast differentiation and fusion by targeting the 3′ untranslated rgion (UTR) of Igf2bp3. Notably, the impacts of miR-6240 mimics on myoblast proliferation, differentiation, and fusion can be effectively counteracted by the overexpression of Igf2bp3. Moreover, our findings elucidate a direct interaction between Igf2bp3 and the myoblast fusion factor myomaker (Mymk). Igf2bp3 binds to Mymk to enhance its mRNA stability. This interaction results in increased expression of Mymk and heightened myoblast fusion. Conclusions Our study unveils Igf2bp3 as a novel post-transcriptional regulator of myoblast fusion through the miR-6240/Mymk axis, significantly contributing to our understanding of skeletal muscle development. Graphical Abstract

show abstract

The miR151 and miR5100 Transfected Bone Marrow Stromal Cells Increase Myoblast Fusion in IGFBP2 Dependent Manner

Cited by 3 publications

References 62 publications

Comparison of Muscle Regeneration after BMSC-Conditioned Medium, Syngeneic, or Allogeneic BMSC Injection

Comparison of Muscle Regeneration after BMSC-Conditioned Medium, Syngeneic, or Allogeneic BMSC Injection

Evolutionary analysis and functional characterization reveal the role of the insulin-like growth factor system in a diversified selection of chickens (Gallus gallus)

The miR-6240 target gene Igf2bp3 promotes myoblast fusion by enhancing myomaker mRNA stability

Contact Info

Product

Resources

About